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Download Our job is only to produce and market innovative tools for physicians. They then identify and define the best way to use our tools. For this reason, we invite you to follow this link to visit the "Physician & Patient Support" page of the Progastrin Cancer Control Association 's website, an association of healthcare professionals that collects, enhances and diffuses knowledge about hPG80 and its usefulness in the fight against cancer. ​ Documents presently available : White paper on the link between hPG 80 (circulating Progastrin) and cancer Physicians' booklet Leaflet for doctors to give to their patients General and pathological data sheets

From Progastrin to hPG 80 A clarification was needed regarding the name of progastrin, a protein most of the time associated to its historical function as the gastrin precursor when it is intracellular. When it is extracellular (the case for cancer patients), it is no more a precursor of gastrin, it becomes oncogenic and tumor promoter. We decided to name extracellular progastrin hPG80 to avoid confusion. ​ 1905>1987: From Gastrin to Progastrin Identification of the intracellular precursor of Gastrin ​ The story of progastrin started with the discovery of gastrin in 1905 when John Sydney Edkins showed the existence of a hormone responsible for gastrin acid secretion. This hormone was called gastric secretin, or gastrin. ​ But it is only in 1987 and 88 that the precursor of gastrin was identified and labelled as progastrin, because of its role as a pro-hormone. It is an 80 amino-acid peptide, processed in the endoplasmic reticulum, with gastrin being the final active product of progastrin maturation. ​ In physiology, progastrin is mainly expressed in the stomach, where gastrin is secreted from the G cells of the antrum. The major function of gastrin is to regulate acidic secretion. ​ Therefore, for years, progastrin was only known as the precursor of gastrin. ​ ​ 1990>2020: From the gastrin precursor to the oncogenic tumor promoter Extracellular, "Progastrin" is no longer the precursor of Gastrin, it is an oncogenic protein. ​ In 1990, the first link of progastrin with tumor cells was done. Bardram was the first to hypothesize that “a low degree of processing of progastrin could serve as a predictor of a malignant clinical course at an early stage of the disease” (Bardram, 1990). ​ And this is where the story of progastrin starts, independently of that of gastrin. ​ Progastrin was shown to be poorly processed in colorectal cancer (Ciccotosto, 1995; Finley et al., 1993; Imdahl et al., 1995; Kochman et al., 1992; Nemeth et al., 1993; Singh, 1994; Van Solinge et al., 1993b). And soon after, Singh et al demonstrated that progastrin was secreted from these cells cultured in vitro, opening the door to the analysis of a functional autocrine/ paracrine function of progastrin in tumor cells (Singh, 1994; Van Solinge et al., 1993b). Colorectal cancers are not the only cancer type to express progastrin. Ovarian cancers do it also (van Solinge et al., 1993a) as well as liver tumors that express precursor forms of gastrin, in particular progastrin unlike normal liver (Caplin et al., 1999). Pancreatic tumors also express the gastrin gene, with 91% of the tumors with the unprocessed progastrin product (Caplin, 2002). ​ The evidence showing that progastrin could be detected and quantified in the blood of colorectal cancer patients was demonstrated by Siddheshwar et al as early as 2000 (Siddheshwar et al., 2000), later confirmed by Prieur et al (2017). It was also demonstrated that progastrin had to be released from tumor cells in order to exert its oncogenic functions. ​ The presence of progastrin in the blood of cancer patients was extended to 11 different cancers (You et al, 2020), highlighting the potential that progastrin may have in cancer pathology. ​ Early 2020: From Progastrin to hPG80 The protein is changing its name to put an end to the confusion that gives rise to misconceptions. ​ However, the cancer community does not acknowledge progastrin as a cancer target by itself due to its name, progastrin, which always brings us back to the past, progastrin as the precursor of gastrin. Moreover, this misunderstanding is accentuated by the almost systematic confusion with a totally different peptide that is phonetically identical, the Pro-Gastrin Releasing Peptide (proGRP), which can be found in the scientific literature under several spellings (with or without a hyphen in progastrin or sometimes even under the name pre-progastrin releasing peptide...). Thus to date, more than half of the results concerning Progastrin on search engines concern this peptide and not the 80 amino acid molecule encoded by the GAST gene. ​ This is where the story of the hPG80 begins. ​ Also, in order to clearly distinguish: intracellular progastrin, the precursor to gastrin, extracellular progastrin (hPG80) which exerts oncogenic functions on tumor cells once released from the tumor cells, pro-gastrin releasing peptide (proGRP), we have been using the name hPG80 since the beginning of 2020 and the publication You et al. to unambiguously refer to the circulating Progastrin historically mentioned in the scientific literature under the single name Progastrin. ​ “h” means human, “PG” means Progastrin and “80” corresponds to the number of amino acids of this protein. ​ This is where the story of hPG80 starts: in order to clearly distinguish between progastrin as the precursor of gastrin and progastrin that exerts oncogenic functions on tumor cells once released from tumor cells, we proposed to rename progastrin once released from tumor cells as hPG80. ​ Today, hPG80 is the circulating progastrin, detected in the blood of patients with multiple cancers and exerting major oncogenic functions, the most relevant being that it is required for cancer stem cells survival. ​ Please note that for greater clarity on this site, we now use the name hPG80, referring to extracellular Progastrin.

About Us Our Mission In the battle against cancer, BIODENA CARE considers its mission as a succession of relays between Fundamental Scientific Knowledge on the one hand and "the Art and Science of Medicine" on the other. The final relay, undoubtedly the most important, is the one that the Physician must carry out alone with his Patient, against the disease. This is why, in order to never forget the Patient, we carry out our mission by exclusively serving Physicians with a single objective: « To ensure that demonstrations of basic science become effective, reliable and accessible solutions, handed over to physicians for the benefit of their patients. » Executive Team Nassima Mimoun Managing Director Skills Medical Doctor MBA from an international Business school in Paris ESCP Business School Harvard Business School: Executive Leadership Program Professional strength 25 years of experience in Pharma Industry Broad range of experiences across various therapeutic areas at regional and local level in multiple markets and mainly in oncology Solid experience in launching and successfully commercializing innovative products and identifying life cycle management opportunities Ability to work successfully with external stakeholders by integrating their insights Strong learning agility and a good track record in coming into new and challenging situations in both, strategic and operational roles using strong communication and interpersonal skills Diversity & Inclusion as a DNA to build right teams and talents working cross functionally Acting & leading by example. Supporting and driving transformations with flexibility and adaptability. Alexandre Prieur Chief Scientific Officer Skills Scientific Director since 2012 20 years in cancer research 8 years of R&D specific to hPG80 (extra-cellular circulating progastrin) PhD in Oncology since 2005 (Paris XI University) Master - Innovation, Valorization, Partnerships (Montpellier University) in 2013 Professional strength 12 years of fundamental research as a researcher in cancer research institutes in Europe 8 years of R&D in biotechnology companies as Chief Scientific Officer (diagnostic and therapy) ​ Results​ Listed as inventor for 8 patent applications, including 7 on interaction between hPG80 and cancer Author of 10+ publications in peer-reviewed journals in the field of cancer Co-editor at Frontiers in Oncology on the Research Topic “Therapeutic Targeting of Cancer Stem Cells- The Current State of the Art “ in 2019 ​ François Fabre Chief Financial and Operationnal Officer Skills Administrator of the group entities Fundraising lead Specialist in business management Master's degree in international business ​ Professional strength 8 years as managing director or general manager of companies 5 years in cash and investment management ​ Results Fundraising actions up to 26 M € Drastic cost management to ensure the sustainability of this company Monica Cappellini Laboratory Manager Skills 7 years of experience in R&D and production specific to hPG80 PhD in Neuroscience (University of Montpellier) ​ Professional strength 19 years of experience in start-up companies as in vivo and/or laboratory manager. Strong team management and project management Implementation and maintenance of quality system according to ISO 13485 ​ Results Co-author in several articles related to hPG80 Successful launch of the DxPG80 kit ​ Our History Our History The dream of a scientist, the fight of a woman Dominique Joubert is a scientist with a PhD in biology, coming from academic and fundamental research in which she worked for more than 40 years, including two decades from 1991 to 2011 as Director of Research at Inserm (France) and Director of the Oncology Department of the IGF, a CNRS-INSERM-University of Montpellier Joint Research Unit. ​ Contrary to scientific dogma, she has always been convinced that cancer responds to the "laws of the living" and is therefore reversible. She is therefore naturally looking for the "key" to this reversion. ​ In 2003, in her laboratory, her team and herself observed a protein that needs to come out of the tumor cell and re-interact with it to exert its effects on the tumor cell. ​ She believes that this protein, resulting from a set of disorders linked to the Wnt signaling pathway (highly involved in tumorigenesis), may be the key she is looking for. ​ She is modeling an experiment to demonstrate that neutralizing this protein can regulate the pathway that generated it. This approach seemed absurd to her team. Neutralizing the product of a mechanism to regulate the said mechanism, the idea is far-fetched! ​ To the surprise of sceptics, the experiment is conclusive, demonstrating for the first time that the tumor mechanism can be reverted into a solid tumor. ​ In a healthy individual, this protein, progastrin, is the precursor of gastrin, it is present in the G cells of the stomach, it is not found in the blood. In a patient with cancer (any cancer to date), it is secreted by the tumor cell of the organ affected by this cancer, it is then called hPG80. We’ve so far detected hPG80 in the blood of 83% cancer patients. Moreover, 100% of tumors produce hPG80[1]. ​ Dominique Joubert now knows that what has just been proven will simply change the history of cancer! She also knows that there is another equally challenging round ahead: bringing together all the energy, resources and expertise needed to ensure that a demonstration of basic research is translated into solutions for physicians, for the benefit of patients. ​ [1]. You et al, EBioMedicine, 2020 Jan;51:102574

hPG80 ​ A New Blood Biomarker to Help Monitoring Tumor Activity for Multiple Cancers What is hPG80? hPG80 in Cancer Evolution Involvement of the Wnt pathway in tumorigenesis hPG 80, the biomarker of tumoral activity ​ Learn more about performances of hPG80 1 What is hPG80? Progastrin is an intracellular protein that is, or not, maturated into gastrin. Non Pathologic Condition Progastrin is not found in the blood of healthy people. When progastrin is maturated into gastrin, it is released from the cells. ​ When gastrin is produced by the G cells of the stomach antrum, it plays its role to control acidic secretions during digestion. Pathologic Condition When progastrin is not maturated into gastrin, it is released from the cells as such and named hPG 80 . ​ This only happens in tumor cells, whatever the tumor cell: progastrin becomes a circulating protein, hPG 80 , which can be detected in the blood of cancer patients. hPG80 (circulating progastrin) is detected in the blood of cancer patients. The ROCHE laboratory markets a test for the detection of Progastrin-releasing peptide (Pro-GRP) to differentiate between 2 types of lung cancer. hPG80 (Progastrin) and Progastrin-releasing peptide (Pro-GRP) are two completely different proteins even though they share the word "Progastrin / Pro-Gastrin” with the same phonetics. 1. What is hPG80? 2 hPG80 in cancer evolution The biomarker hPG80 is present in the tumor / bloodstream of cancer patients at all stages of tumor progression, from primary tumor to metastasis. Example of CRC 2. hPG80 in cancer evolution 3 Involvement of the Wnt pathway in tumorigenesis 3.1 Activation – Non activation of Wnt/ß-Catenin Pathway The Wnt signaling pathway is an evolutionarily conserved signal transduction pathway that regulates a wide range of cellular functions during development and adulthood. It controls multiple aspects of development, including cell proliferation, cell fate determination, apoptosis, cell migration and cell polarity during development and stem cell maintenance in adults. Inappropriate activation of the Wnt pathway is also a major factor in human oncogenesis (Ng et al, Cells, 2019). Normal Cell: ON Normal Cell: OFF 3.2 An early event in cancer development Chronic activation of the Wnt/ß-catenin pathway is a central mechanism in cancer biology that is implicated in: Induction of cellular proliferation and blocking of differentiation leading to primary tumor growth, Induction of epithelial mesenchymal transition (EMT) leading to metastasis formation, Regulation of cancer stem cell pathways leading to chemoresistance and relapse. 3.3 hPG80: the gene GAST coding for hPG80 is a direct Wnt/ß-catenin Target Gene In normal cells: Tunable (On/Off) activation of the Wnt/ß-catenin target genes. In cancer cells: Constitutively activated Wnt/ß-catenin pathway leads to continuous expression of the gene GAST coding for hPG80 and secretion of hPG80. Tumor Cell: always ON 3. Involvement of Wnt pathway 4 hPG80, the biomarker of tumoral activity Cancer stem cells (CSCs) play an important role in tumor initiation and progression. ​ CSCs are cells within a tumor that possess the capacity to self-renew, to give rise to the heterogeneous lineages, to be resistant to standard therapy and to initiate tumor recurrence and metastasis (Curtin el al, Oncotarget 2010). ​ CSCs need hPG80 for their survival (Giraud et al, Cancer Research, 2016; Prieur et al, Clin Cancer Research, 2017). ​ CSCs secrete 100 to 1000 more of hPG80 than non-CSC cancer cells (Prieur et al, Clin Cancer Research, 2017). Secreted hPG80 maintains the stemness of CSCs (Prieur et al, Clin Cancer Research, 2017). ​ Neutralization of secreted hPG80 by a therapeutic antibody decreases CSCs frequency, metastatic seeding, increases chemosensitivity and delays relapses (Prieur et al, Clin Cancer Research, 2017). 4. hPG80, the biomarker of tumoral activity Learn more... about hPG80 Performances

Publications Last Posters hPG80 Main Scientific Publications Last updated: Jully 2, 2021 Publications Prognostic Value of Plasma hPG 80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma ​ Jan, 2021 Simple Summary Metastatic renal cell carcinoma (mRCC) accounts for one-third of all newly diagnosed renal cell cancers. A better understanding of the biology and molecular basis of disease progression has resulted in several drug targets being identified and led to approval of several new drugs for treating mRCC in the past decade. A growing need has emerged for identifying novel molecular tumor biology based and stage-specific prognostic and predictive biomarkers in mRCC reflective of biology beyond the currently available prognostic models which are solely based on clinical characteristics. We investigated hPG 80 (circulating progastrin), which is associated with kidney cancer biology and found that hPG 80 levels is both an independent prognostic marker in mRCC and also improves current clinical prognostic models. This will help stratify mRCC patients more accurately in future and improve the management of mRCC patients. Abstract Precise management of kidney cancer requires the identification of prognostic factors. hPG 80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG 80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG 80 levels on overall survival (OS) in mRCC patients after controlling for hPG 80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG 80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG 80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG 80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG 80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG 80 levels (score of 1 for patients having hPG 80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG 80 levels within these subgroups, increased OS were observed in patients with low hPG 80 levels (<4.5 pM). In conclusion, our data suggest that hPG 80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients. Manish Kohli 1,*, Winston Tan 2, Bérengère Vire 3, Pierre Liaud 3, Mélina Blairvacq 3, Frederic Berthier 4, Daniel Rouison 4, George Garnier 4, Léa Payen 5, Thierry Cousin 6, Dominique Joubert 6 and Alexandre Prieur 6,* + Journals - Cancers - Volume 13 - Issue 3 - 10.3390/cancers13030375 The oncogenic and druggable hPG 80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients ​ Dec, 2019 EBiomedicine by THE LANCET déc. 2019 Authors : Benoit You Frédéric Mercier Eric Assenat Carole Langlois-Jacques Olivier Glehen Julien Soulé et al. In colorectal cancer, hPG80 (progastrin) is released from tumor cells, promotes cancer stem cells (CSC) self-renewal and is detected in the blood of patients. Because the gene GAST that encodes hPG80 is a target gene of oncogenic pathways that are activated in many tumor types, we hypothesized that hPG80 could be expressed by tumors from various origins other than colorectal cancers, be a drug target and be detectable in the blood of these patients. […] Research in context Evidence before study The National Cancer Institute recently highlighted the need forbiomarkers to improve early detection of cancers, monitor treatment effects and detect disease relapses. Therefore, the identification of a new tumor blood-based marker with broad expression across tumor types might have a significant impact on diagnostic and follow-up of patients. hPG80 (progastrin) was shown to be over-expressed in human colorectal tumor cells. Interestingly, GAST is a direct target of the Wnt/ß-catenin/Tcf4 oncogenic pathway. Since this pathway is activated inmany other cancers and plays a major function in cancer stem cells survival, we hypothesized that hPG80 (i) might be expressed by other types of cancers, and would be present in the blood of patients with tumors different from colorectal cancers and (ii) might be a drug target for various type of cancers. ​ Added value of this study Here we show that hPG80 is expressed by the tumor and present in the blood of 11 different types of cancer patients. Two retrospective kinetic studies where blood samples were collected regularly from cancer patients undergoing different treatments revealed strong associations between longitudinal hPG80 . ..... concentrations and anti-cancer treatment efficacy. We provide data showing the decrease of hPG80 after surgery in a cohort of patients with peritoneal involvements from gastroin-testinal cancers, treated with peri-operative chemotherapy regimens and cytoreductive surgery. We also show the correlationbetween hPG80 levels and standard imaging in a cohort of patients with hepatocellular carcinoma, managed with local or systemic treatments, including patients with no detectable levels of alpha-fetoprotein. Finally, we show that targeting hPG80 with our humanized antibody decreases self-renewal capacity of cancer stem cells from various origins. ​ Implications of all available evidence The technology we developed to detect hPG80 in the blood isr obust, reliable and inexpensive, making this test easy to implement by oncologists. This technology could be used to improve early cancer diagnosis and treatment efficacy monitoring. Furthermore, in this study we show that our anti-hPG80 therapeutic antibody, that was initially found to target the Wnt pathway and decrease self-renewal capacity in cancer stem cells from colorectal cancer, is envisioned to have the same effect on tumors from other origins. + Direct Comparison of Diagnostic Performance of 9 Quantitative Fecal Immunochemical Tests for Colorectal Cancer Screening ​ Sep, 2017 Gastroenterology, 2017 September Authors : Anton Gies1, Katarina Cuk2, Petra Schrotz-King1, Hermann Brenner A variety of fecal immunochemical tests (FITs) for hemoglobin (Hb) are used in colorectal cancer screening. It is unclear to what extent differences in reported sensitivities and specificities reflect true heterogeneity in test performance or differences in study populations or varying pre-analytical conditions. We directly compared the sensitivity and specificity values with which 9 quantitative (laboratory-based and point-of-care) FITs detected advanced neoplasms (AN) in a single colorectal cancer screening study. […] + Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. ​ Dec, 2016 JAMA Oncol. 2016 Dec 3. Authors : Global Burden of Disease Cancer Collaboration, Fitzmaurice, Allen, Barber, Barregard, Bhutta, Brenner, Dicker .../... Zaid i, Zaki, Zenebe, Murray, Naghavi. Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. […] + Progastrin a new pro-angiogenic factor in colorectal cancer ​ Jun, 2015 Oncogene. 2015 June Authors : Najib S1, Kowalski-Chauvel A1, Do C1, Roche S2, Cohen-Jonathan-Moyal E3, Seva C1.Angiogenesis is essential in tumor progression and metastatic process, and increased angiogenesis has been associated with poor prognosis and relapse of colorectal cancer (CRC). VEGF has become the main target of anti-angiogenic therapy. However, most patients relapse after an initial response or present a resistance to the treatment. Identification of new pro-angiogenic factors may help to improve anti-angiogenic therapy. In this study, we demonstrated that the pro-hormone progastrin (PG), over-expressed in[…] + Wnt Signaling in Cancer ​ May, 2012 Cold Spring Harb Perspect Biol. 2012 MayAuthors : Paul PolakisAberrant regulation of the Wnt signaling pathway is a prevalent theme in cancer biology. From the earliest observation that Wnt overexpression could lead to malignant transformation of mouse mammary tissue to the most recent genetic discoveries gleaned from tumor genome sequencing, the Wnt pathway continues to evolve as a central mechanism in cancer biology. This article summarizes the evidence supporting a role for Wnt signaling in human cancer. This includes a review of […] + Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis ​ Aug, 2000 J Clin Invest. 2000 August Authors : Theodore J. Koh,1 Clemens J. Bulitta,1 John V. Fleming,1 Graham J. Dockray,2 Andrea Varro,2 and Timothy C. Wang1Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene occur in most colorectal cancers and lead to activation of β-catenin. Whereas several downstream targets of β-catenin have been identified (c-myc, cyclin D1, PPARδ), the precise functional significance of many of these targets has not been examined directly using genetic approaches. Previous studies have shown that […] + Targeting the Wnt pathway and cancer stem cells with anti-progastrin humanized antibodies: a major breakthrough for K-RAS mutated colorectal cancer treatment ​ Jun, 2017 Clinical Cancer Research, 2017 JuneAuthors : Alexandre Prieur, Monica Cappellini, Guillaume Habif, Marie-Paule Lefranc, Thibault Mazard, Eric Morency, Jean-Marc Pascussi, .../... Chris Planque, Eric Assenat, Frédéric Bibeau, Jean-François Bourgaux, Pascal Pujol, Alain Sézeur, Marc Ychou and Dominique JoubertPatients with metastatic colorectal cancer (CRC) suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for[…] + Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem-like Cells. ​ Jun, 2016 Cancer Res. 2016 June Authors : Giraud, Failla, Pascussi, Lagerqvist, Ollier, Finetti, Bertucci, Ya, Gasmi, Bourgaux, Prudhomme, Mazard, Ait-Arsa, Houhou, Birnbaum, Pélegrin, Vincent, Ryall, Joubert, Pannequin, Hollande.Subpopulations of cancer stem-like cells (CSC) are thought to drive tumor progression and posttreatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable proportions of self-renewing CSC within heterogeneous tumors under homeostatic conditions remain poorly understood. Progastrin is a secreted peptide that exhibits tumor-forming potential in colorectal cancer, where it regulates pathways known to modulate colon CSC behaviors. In this study, we investigated the role of progastrin in […] + Novel roles of gastrin ​ Jul, 2014 J Physiol. 2014 Jul 15Authors : Dimaline, VarroThe existence of the hormone gastrin in the distal stomach (antrum) has been known for almost 110 years, and the physiological function of this amidated peptide in regulating gastric acid secretion via the CCK2 receptor is now well established. In this brief review we consider important additional roles of gastrin, including regulation of genes encoding proteins such as […] + The wnt target jagged-1 mediates the activation of notch signaling by progastrin in human colorectal cancer cells. ​ Aug, 2009 Cancer Res. 2009 August Authors : Julie Pannequin, Caroline Bonnans, Nathalie Delaunay, Joanne Ryan, Jean-François Bourgaux, Dominique Joubert and Frédéric Hollande The Wnt and Notch signaling pathways are both abnormally activated in colorectal cancer (CRC). We recently showed that progastrin depletion inhibited Wnt signaling and increased goblet cell differentiation of CRC cells. Here, we show that progastrin down-regulation restores the expression by CRC cells of the early secretory lineage marker Math-1/Hath-1 due to […] + Expression but incomplete maturation of progastrin in colorectal carcinomas ​ Apr, 1993 Gastroenterology. 1993 April Authors : Van Solinge WW1, Nielsen FC, Friis-Hansen L, Falkmer UG, Rehfeld JF.To evaluate the hypothesis that gastrin is a local growth factor in colonic carcinomas, the expression of gastrin messenger RNA (mRNA) and peptides were examined in five human colon carcinoma cell lines, 12 solid colon carcinomas, and normal colonic tissue... […] + Common pitfalls in preclinical cancer target validation ​ May, 2017 Nature reviews, 2017 May Authors : William G. Kaelin JrAn alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being misled by off-target effects when using pharmacological or genetic perturbants in complex biological assays. This danger is particularly acute when, as is often the case in cancer pharmacology, the biological phenotype being measured is a […] + The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies ​ Feb, 2016 Lab Invest. 2016 February Yang, Wang, Zhang, Wang, Nan, Li, Zhang, Mohammed, Haydon, Luu, Bi, He.he canonical WNT/β-catenin signaling pathway governs a myriad of biological processes underlying the development and maintenance of adult tissue homeostasis, including regulation of stem cell self-renewal, cell proliferation, differentiation, and apoptosis. WNTs are secreted lipid-modified glycoproteins that act as short-range ligands to activate receptor-mediated signaling pathways. The hallmark of the […] + Gastric secretion ​ Nov, 2013 Curr Opin Gastroenterol. 2013 NovAuthors : Shijian Chu;Mitchell Schubert;The review summarizes the past year's literature, basic science and clinical, regarding the neural, paracrine, hormonal, and intracellular regulation of gastric acid secretion.[…] + Beta-catenin/Tcf-4 inhibition after progastrin targeting reduces growth and drives differentiation of intestinal tumors ​ Nov, 2007 Clinical Cancer Research, 2017 JuneAuthors : Alexandre Prieur, Monica Cappellini, Guillaume Habif, Marie-Paule Lefranc, Thibault Mazard, Eric Morency, Jean-Marc Pascussi, .../... Chris Planque, Eric Assenat, Frédéric Bibeau, Jean-François Bourgaux, Pascal Pujol, Alain Sézeur, Marc Ychou and Dominique JoubertPatients with metastatic colorectal cancer (CRC) suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for[…] + A synthesis of the knowledge of progastrin is available on the website of the Progastrin cancer control association. . + Posters hPG80 Last Posters 2021 ANNUAL MEETING Poster Session : Prognostic value of plasma hPG80, alone or in combination with AFP in patients with hepatocellular carcinoma + Download the Poster 2020 Gastro Intestinal Cancers Symposium 628 Poster Session (Board #G9 ) : HPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms. + Download the Poster 2019 ANNUAL MEETING 2294 / 23 - Plasma progastrin level as a predictive and prognostic biomarker in advanced prostate cancer + Download the Poster 2021 ANNUAL MEETING Plasma hPG80 (circulating Progastrin) levels in cancer patients in Nigeria: Prolevcan study + Download the Poster 2019 ANNUAL MEETING 3037 / 29 - Progastrin, a novel ubiquitous cancer blood biomarker for early detection and monitoring. + Download the Poster 2019 ANNUAL MEETING 2222 / 11 - Progastrin a new biomarker for hepatocellular cancer patient follow-up + Download the Poster 2021 ANNUAL MEETING Poster Session : hPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms. + Download the Poster 2019 ANNUAL MEETING 2289 / 18 - Prognostic impact of progastrin levels in blood compared to MSKCC based clinical prognosis in metastatic renal cell cancer patients + Download the Poster 2018 ANNUAL MEETING 119P - Progastrin, a new blood biomarker for the diagnostic and therapeutic monitoring, in G.I. cancers: A BIG-RENAPE project. + Download the Poster

hPG80 Performances A performing biomarker. Present at all stages and for Multiple Cancer Types. 1 Healthy Blood Donors vs All Combined Cancers Significant increase in hPG 80 levels in all cancer patients (N= 1267, Median hPG 80 = 4.77 pM) compared to healthy blood donors (N=557 for 18-70 yo, Median hPG 80 = 1.05 pM and N=137 for 18-25 yo, Median hPG 80 = 0.2 pM). You B, Mercier F, Assenat E, et al : The oncogenic and druggable hPG80 is overexpressed in multiple cancers and detected in the blood of patients. EBioMedicine 51:102574, 2020 1. Healthy Blood Donors vs All Combined Cancers 2 Diagnostic des performances de hPG80 par types de tumeurs Progastrin, a Novel Ubiquitous Cancer Blood Biomarker for Early Detection and Monitoring. Benoit You, Eric Assenat, Olivier Glehen, Delphine Maucort-Boulch, Léa Payen, Vahan Kepenekian, Marie Dupuy, Pierre Liaud, Thibault Mazard, Gwenaël Ferron, Maud Flacelière, Julien Soulé, Véronique Saywell, Fanny Belouin, Winston Tan, Laurent Villeneuve, Marc Ychou, Manish Kohli, Dominique Joubert and Alexandre Prieur. ASCO 2019 - Poster #3037. 2. Diagnostic performances of hPG80 per Tumor types 3 Performances of hPG80 vs Existing Tumor Markers BREAST CANCER Diagnostic efficacy of CA 15-3 and CEA in the early detection of metastatic breast cancer – A retrospective analysis of kinetics on 743 breast cancer patients. Stieber P et al., Clin Chim Acta., 2015. Progastrin, a Novel Ubiquitous Cancer Blood Biomarker for Early Detection and Monitoring. Benoit You, Eric Assenat, Olivier Glehen, Delphine Maucort Boulch, Léa Payen, Vahan Kepenekian, Marie Dupuy, Pierre Liaud, Thibault Mazard,Gwenaël Ferron, Maud Flacelière, Julien Soulé, Véronique Saywell, Fanny Belouin, Winston Tan, Laurent Villeneuve, Marc Ychou, Manish Kohli, Dominique Joubert and Alexandre Prieur. ASCO 2019 - Poster #3037. N=53 patients. N=9 patients, work ongoing. COLORECTAL CANCER CEA Monitoring in Colorectal Cancer. Fakih MG, Padmanabhan A., Oncology (Williston Park), 2006. Cutoff at 5 ng/mL. Direct Comparison of Diagnostic Performance of 9 Quantitative Fecal Immunochemical Tests for Colorectal Cancer Screening. Gies A et al., Gastroenterology, 2018. Progastrin, a Novel Ubiquitous Cancer Blood Biomarker for Early Detection and Monitoring. Benoit You, Eric Assenat, Olivier Glehen, Delphine Maucort-Boulch, Léa Payen, Vahan Kepenekian, Marie Dupuy, Pierre Liaud, Thibault Mazard, Gwenaël Ferron, Maud Flacelière, Julien Soulé, Véronique Saywell, Fanny Belouin, Winston Tan, Laurent Villeneuve, Marc Ychou, Manish Kohli, Dominique Joubert and Alexandre Prieur. ASCO 2019 - Poster #3037. N = 98 patients. N = 192 patients. HEPATOCELLULAR CARCINOMA Serum tumor markers for detection of hepatocellular carcinoma. Zhou L et al., World J Gastroenterol., 2006. Progastrin, a Novel Ubiquitous Cancer Blood Biomarker for Early Detection and Monitoring. Benoit You, Eric Assenat, Olivier Glehen, Delphine Maucort-Boulch, Léa Payen, Vahan Kepenekian, Marie Dupuy, Pierre Liaud, Thibault Mazard, Gwenaël Ferron, Maud Flacelière, Julien Soulé, Véronique Saywell, Fanny Belouin, Winston Tan, Laurent Villeneuve, Marc Ychou, Manish Kohli, Dominique Joubert and Alexandre Prieur. ASCO 2019 - Poster #3037. N = 27 patients. N = 65 patients. hPG 80 has a better sensitivity to detect HCC than AFP. AFP was above 20ng/ml in 54.3% of the samples while hPG 80 (circulating progastrin) was detected in 80.2% (threshold = 1pM). ​ Progastrin a new biomarker for hepatocellular cancer patient follow-up. Alexandre Prieur, Marie Dupuy, Pierre Liaud, Dominique Joubert and Eric Assenat. AACR 2019 - Poster #2222. OVARIAN CANCER Clinical analysis of four serum tumor markers in 458 patients with ovarian tumors: diagnostic value of the combined use of HE4, CA125, CA19-9, and CEA in ovarian tumors. Chen F et al., Cancer Manag Res, 2018. Progastrin, a Novel Ubiquitous Cancer Blood Biomarker for Early Detection and Monitoring. Benoit You, Eric Assenat, Olivier Glehen, Delphine Maucort-Boulch, Léa Payen, Vahan Kepenekian, Marie Dupuy, Pierre Liaud, Thibault Mazard, Gwenaël Ferron, Maud Flacelière, Julien Soulé, Véronique Saywell, Fanny Belouin, Winston Tan, Laurent Villeneuve, Marc Ychou, Manish Kohli, Dominique Joubert and Alexandre Prieur. ASCO 2019 - Poster #3037. N = 27 patients. N = 181 patients. PROSTATE CANCER A review on the clinical Utility of PSA in Cancer Prostate. Adhyam M, Gupta AK; Indian J Surg Oncol, 2012. PSA cutoff at 4 ng/mL. Progastrin, a Novel Ubiquitous Cancer Blood Biomarker for Early Detection and Monitoring. Benoit You, Eric Assenat, Olivier Glehen, Delphine Maucort-Boulch, Léa Payen, Vahan Kepenekian, Marie Dupuy, Pierre Liaud, Thibault Mazard, Gwenaël Ferron, Maud Flacelière, Julien Soulé, VéroniqueSaywell, Fanny Belouin, Winston Tan, Laurent Villeneuve, Marc Ychou, Manish Kohli, Dominique Joubert and Alexandre Prieur. ASCO 2019 - Poster #3037. N = 93 patients. N = 444 patients. 3. Performances of hPG80 vs Existing Tumor Markers 4. hPG80 for the monitoring of Minimal Residual Disease and Response to Treatment 4 hPG80 for the monitoring of Minimal Residual Disease and Response to Treatment PERITONEAL CARCINOMATOSIS A cohort of patients with peritoneal involvements from gastrointestinal cancers, treated with peri-operative chemotherapy regimens and cytoreductive surgery (Lyon, France, NCT02823860). Global analysis. High levels of hPG80 before surgery. Decrease of hPG80 8h to 24h after surgery (From 3.08 pM to 1.57 pM; p=0.035). Individual analysis. 74.2% of the patients had a decrease of at least 25% of hPG80 levels after surgery. Sustained elevations in hPG80 concentrations after surgery could be suggestive of the presence of residual disease. You B, Mercier F, Assenat E, et al : The oncogenic and druggable hPG 80 is overexpressed in multiple cancers and detected in the blood of patients. EBioMedicine 51:102574, 2020 Gilles Freyer, Delphine Maucort-Boulch, Dominique Joubert and Olivier Glehen. ESMO 2018 - Poster # 1953. PROSTATE CANCER Elevated hPG80 levels in patients with advanced prostate cancer (aPCa)* (healthy blood donors 18 to 40 yo: median hPG80 = 0.37 pM vs aPCa: median hPG80 = 4.7 pM, p<0.0001). *aPCa includes metastatic hormone sensitive (mHSPC) and metastatic castration resistant (mCRPC) prostate cancer patients. Overall survival (OS) according to hPG80 levels evolution during follow-up. Patients with a serial increase of hPG80 had a worst overall survival compare to the other group (9.3 yo vs 12.4 yo, P = 0.019). Plasma Progastrin Level As A Prognostic Biomarker In Advanced Prostate Cancer. Manish Kohli, Winston Tan, Léa Payen, Carole Langlois-Jacques, Pierre Liaud, Delphine Maucort-Boulch, Dominique Joubert and Alexandre Prieur. AACR 2019 - Poster #2294. KIDNEY CANCER Elevated hPG80 levels in patients with metastatic renal cell carcinoma (mRCC) (Cohort (healthy blood donors18-25 y/o): median hPG80 = 0.29 pM vs mRCC hPG80= 7.2 pM). We compared hPG80 levels with the MSKCC prognostic criteria for patient survival. In this score, patients are separated in 3 groups: good, intermediate and poor prognostic. hPG80 levels were higher within the MSKCC score poor prognostic group (p<0.001) (median 30.39 pM vs 6 pM and 9.34 pM in the good and intermediate group, respectively). hPG80 assay might be useful for defining subsets of mRCC patients with poor survival who need to be treated aggressively. Prognostic Impact Of Progastrin Levels In Blood Compared To MSKCC Based Clinical Prognosis In Metastatic Renal Cell Cancer Patients. Manish Kohli, Winston Tan, Léa Payen, Carole Langlois-Jacques, Pierre Liaud, Delphine Maucort-Boulch, Dominique Joubert and Alexandre Prieur. AACR 2019 - Poster #2289. 5 hPG80 for the Monitoring of Relapse (Tumor Activity) MONITORING FOR HEPATOCELLULAR CARCINOMA RECURRENCE Earlier detection of small lesions and the monitoring of recurrence may be improved with hPG80 as a supplemental blood-based biomarker, especially in AFP negative populations where there is limited information. Patients in remission following disease management have lower hPG80 concentrations compared to active cancers. 76% of patients with progressing disease during or after treatment had an increased hPG80 > 25%. Illustrative hPG80 longitudinal changes around and during disease management (baseline; remission; progression), with associated imaging obtained at the same times in a typical patient. Progastrin a new biomarker for hepatocellular cancer patient follow-up. Alexandre Prieur, Marie Dupuy, Pierre Liaud, Dominique Joubert and Eric Assenat. AACR 2019 - Poster # 2222. You B, Mercier F, Assenat E, et al : The oncogenic and druggable hPG80 is overexpressed in multiple cancers and detected in the blood of patients. EBioMedicine 51:102574, 2020. MONITORING FOR OVARIAN CANCER RECURRENCE 70% of ovarian cancers are not diagnosed until stage III or IV where survival rates are low (48% after 5 years). As a result, cancer recurrence is high (70-95%) following standard treatment by surgery and combination chemotherapy. hPG80, as a blood-based biomarker used in conjunction with CA125, could improve the early detection of residual disease, treatment efficacy, and/or relapse following treatment. Progastrin, a Novel Ubiquitous Cancer Blood Biomarker for Early Detection and Monitoring. Benoit You, Eric Assenat, Olivier Glehen, Delphine Maucort-Boulch, Léa Payen, Vahan Kepenekian, Marie Dupuy, Pierre Liaud, Thibault Mazard, Gwenaël Ferron, Maud Flacelière, Julien Soulé, Véronique Saywell, Fanny Belouin, Winston Tan, Laurent Villeneuve, Marc Ychou, Manish Kohli, Dominique Joubert and Alexandre Prieur. ASCO 2019 - Poster #3037. Learn more... about hPG80 Main Scientific Publications

​ DxPG 80 HOW-TO GUIDE (FRANCE) Human circulating Progastrin (hPG80) Immunoassay ​ ​ ​ The DxPG80 Elisa test DxPG80 IVD test how-to guide Prescription​ ​ Last updated: August 3, 2020 Access to this page is restricted to healthcare professionals only The DxPG 80 test is an ELISA (Enzyme-Linked Immunosorbent Assay) for the detection of hPG 80 (circulating human progastrin). The test is intended for professional laboratory use only. ​ Please note that for greater clarity, we use the name hPG 80 , referring to extracellular Progastrin. The test is based on the principle of a sandwich ELISA to measure the concentration of hPG 80 in plasma samples that have been collected in EDTA tubes. Briefly, a capture antibody specific for hPG 80 is immobilised on the 96-well plate. The hPG 80 present in the calibrators and samples added to the wells will bind to the immobilized capture antibody. The test plate includes calibrators which are used to estimate the level of hPG 80 in EDTA plasma samples. The wells are washed and an anti- hPG 80 detection antibody coupled to horseradish peroxidase (HRP) is added, resulting in an antibody-antigen-antibody complex. After a second wash, a substrate solution of 3,3',5,5'-Tetramethylbenzidine (TMB) is added to the wells, producing a blue colour directly proportional to the amount of hPG 80 present in the initial sample. The Stop Solution changes the colour from blue to yellow, and the wells are read at 450 nm with a microplate reader. The assay is technically characterised in manual mode by a limit of detection (LOD, 1 pM) and a limit of quantification (LOQ, 3.3 pM). The LOD detects the presence of hPG 80 and the LOQ gives the concentration at which the assay is quantitative. ​ Table 1 : Comparative description of hPG 80 in Controls (healthy blood donors 18-40 years old at low risk of cancer) and Cancer patients (16 cancers tested, all combined)[1]. Reference range are given for a 2.5 (low range) and 97.5 (high range) percentile. IQR: Inter-Quartil Range, 25-75%. SE: Standard Error. BIBLIOGRAPHY [1]. You et al, EBioMedicine, 2020 Jan;51:102574 From the blood test to reporting the result to the physician:

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Biodena Care optimizes cancer management A simple and accessible test In 2003, our R&D team discovered the essential role of the hPG80 protein in cancer progression. From this discovery, which came from French research, we developed a practical and affordable blood test: DxPG80. DxPG80: a new device to lead the fight against cancer Through a simple blood test, the DxPG80 test reveals the presence of hPG80, a biomarker specifically associated with cancer diagnosis. See more French research excellence at the service of patients Proposing a more efficient support The reliable and reproducible DxPG80 test contributes to the optimization of the oncology patient journey. The incidence of cancer is growing inexorably, it is time to act practically 19.3 million 28.4 million 200 billion € new cases in 2020 new cases forecasted in 2040 EU and US treatment cost in 2017 Cancer: earlier detection, greater chance of remission Sources : WHO and Cancer Atlas Our ambition: innovation at the service of the patient Tomorrow, we will become a key player in the overall management of cancer patients in termes of: Early diagnosis Localization Therapeutic strategy for patients with a first-in-class therapeutic antibody. Contact us

hPG80 Main Scientific Publications Publications Last Posters Publications hPG80 (circulating progastrin) as a blood biomarker for high-grade glial tumors: A pilot study January 2023 Abstract Background: Currently, the long-term prognosis and survival rate of patients with high-grade glial tumors remains poor and there are no biomarkers. hPG80 (circulating progastrin) secreted into the blood by tumor cells has been widely studied in colorectal cancer. Its involvement in tumorigenesis has been demonstrated in the literature. Moreover, according to a recent study, hPG80 is expressed in the blood of cancer patients at a significantly higher concentration than in the control group composed of healthy blood donors. Methods: The PROGLIO study is a pilot, single-center, longitudinal study that primarily seeks to evaluate circulating plasma hPG80 concentrations over time in patients with high-grade glial tumors. A fasting blood sample will be taken on the start and end day of radiotherapy and during the adjuvant chemotherapy (every 3 cycles). Follow-up monitoring will be performed for 9 months, with a blood sample taken every 3 months on the day of the follow-up MRI. The study plans to recruit 30 patients and recruitment started in February 2022. ​ Trial registration: ClinicalTrials.gov , ID NCT05157594; registered on October 27, 2021. Mélanie Casile; Judith Passildas; Bérengère Vire; Ioana Molnar; Xavier Durando. + Journals - Frontiers, January 11th 2023 hPG80 and cancer: A new blood biomarker in development for patient monitoring June 2022 Abstract Recent technological advances coupled with our improved understanding of the molecular and cellular mechanisms associated with cancer development have enabled better overall patient care. Among the newly identified biomarkers such as circulating tumor DNA or circulating tumor cells, hPG80 (circulating progastrin) that is easy to detect and quantify by a simple ELISA assay has the potential to become a new routine clinical tool in oncology if on-going studies validated its utility. Indeed, on the one hand, hPG80 was found in the blood of patients with different tumors (colorectal, pancreatic, liver, lung, stomach, kidney cancers) at a significantly higher concentration than in healthy donors. Moreover, some studies suggested a potential association between hPG80 concentration changes and anti-cancer treatment efficacy in patients with gastro-intestinal and hepatocellular carcinomas. Finally, hPG80 might be a prognostic factor for overall survival in metastatic renal cell carcinoma cancer (mRCC) and in hepatocellular carcinoma (HCC). If these hypotheses were validated, hPG80 might help better stratify patients according to their prognosis, and also become a tool to monitor relapse and predict treatment response. Prospective validation studies are on-going. Benoit You ; Eric Assenat ; Léa Payen Thibault Mazard ; Olivier Glehen ; Sara Calattini ; Laurent Villeneuve ; Gaëlle Lescuyer ; Bérengère Vire; Marc Ychou. + Journals - Bulletin du Cancer, June 2022, Pages 707-713 hPG80 (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors February 2022 Simple Summary Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. The study demonstrated increased levels of hPG80 in all sub-types of NENs, with a high sensitivity and specificity demonstrated. Plasma hPG80 in NENs may be a diagnostic blood biomarker for both low- and high-grade NENs; further study is warranted. A prospective multi-center trial is ongoing in NET to evaluate hPG80 as a means of monitoring disease (NCT04750954). Abstract Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. Plasma hPG80 was quantified from 95 stage IV NEN patients, using DxPG80technology (ECS Progastrin, Switzerland) and compared with hPG80 concentrations in two cohorts of healthy donor controls aged 50–80 (n = 252) and 18–25 (n = 137). Median hPG80 in NENs patients was 5.54 pM compared to 1.5 pM for the 50–80 controls and 0.29 pM the 18–25 cohort (p < 0.0001). Subgroup analysis revealed median hPG80 levels significantly higher than for either control cohort in neuroendocrine carcinoma (NEC; n = 25) and neuroendocrine tumors (NET; n = 70) including the small-cell lung cancer (SCLC) sub-cohort (n = 13). Diagnostic accuracy, estimated by AUCs, was high for NENs, as well as both sub-groups (NEC/NET) when compared to the younger and older control groups. Plasma hPG80 in NENs may be a diagnostic blood biomarker for both low- and high-grade NENs; further study is warranted. A prospective multi-center trial is ongoing in NET to evaluate hPG80 as a means of monitoring disease (NCT04750954). Aman Chauhan, Alexandre Prieur, Jill Kolesar, Susanne Arnold, Léa Payen, Younes Mahi, Berengere Vire, Madison Sands, B. Mark Evers, Dominique Joubert and Lowell Anthony. + Journals - Cancers 2022, 14, 863 Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma Jan, 2022 Simple Summary Liver cancer is the sixth most common cancer world-wide and hepatocellular carcinoma (HCC), the most common form of primary liver cancer, accounts for 90% of the cases. The diagnosis of HCC is usually based on non-invasive criteria using detection of a liver nodule in abdominal ultrasonography or high serum alpha-fetoprotein (AFP) levels. However, as it is only elevated in 60% of patients with HCC, AFP has limited accuracy, especially in early stages, as both a diagnostic and prognostic test. We investigated hPG80 (circulating progastrin), which is associated with liver cancer biology, and found that hPG80 levels is both an independent prognostic marker in HCC and used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients at early-stage. This will help stratify HCC patients more accurately in the future and improve the management of these patients. Abstract Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80(hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80−) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80−/AFP+ and hPG80−/AFP−, 13.4 months versus not reached respectively, p < 0.0001 and hPG80+/AFP+ and hPG80+/AFP−, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC. Marie Dupuy, Sarah Iltache, Benjamin Rivière, Alexandre Prieur, George Philippe Pageaux, José Ursic Bedoya, Stéphanie Faure, Heloïse Guillaumée and Eric Assenat. + Journals - Cancers 2022, 14(2), 402 ​ A novel method to detect hPG80 (human circulating progastrin) in the blood Sep, 2021 Abstract hPG80 (human circulating progastrin) is produced and released by cancer cells. We recently reported that hPG80 is detected in the blood of patients with cancers from different origins, suggesting its potential utility for cancer detection. To accurately measure hPG80 in the blood of patients, we developed the DxPG80 test, a sandwich Enzyme-Linked Immunosorbent Assay (ELISA). This test quantifies hPG80 in EDTA plasma samples. The analytical performances of the DxPG80 test were evaluated using standard procedures and guidelines specific to ELISA technology. We showed high specificity for hPG80 with no cross-reactivity with human glycine-extended gastrin (hG17-Gly), human carboxy-amidated gastrin (hG17-NH2) or the CTFP (C-Terminus Flanking Peptide) and no interference with various endogenous or exogenous compounds. The test is linear between 0 and 50 pM hPG80 (native or recombinant). We demonstrated a trueness of measurement, an accuracy and a variability of hPG80 quantification with the DxPG80 test below the 20% relative errors as recommended in the guidelines. The limit of detection of hPG80and the limit of quantification were calculated as 1 pM and 3.3 pM respectively. In conclusion, these results show the strong analytical performance of the DxPG80 test to measure hPG80 in blood samples. Cappellini Monica, Flaceliere Maud, Saywell Veronique, Soule Julien, Blanc Emilie, Belouin Fanny, Ortiz Erika, Canterel-Thouennon Lucile, Poupeau Sophie, Tigrett Sylvia, Vire Bérengère, Liaud Pierre, Blairvacq Mélina, Joubert Dominique, Prieur Alexandre + Journals - Analytical Methods - 2021, 13, 4468–4477 Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma ​ Jan, 2021 Simple Summary Metastatic renal cell carcinoma (mRCC) accounts for one-third of all newly diagnosed renal cell cancers. A better understanding of the biology and molecular basis of disease progression has resulted in several drug targets being identified and led to approval of several new drugs for treating mRCC in the past decade. A growing need has emerged for identifying novel molecular tumor biology based and stage-specific prognostic and predictive biomarkers in mRCC reflective of biology beyond the currently available prognostic models which are solely based on clinical characteristics. We investigated hPG80 (circulating progastrin), which is associated with kidney cancer biology and found that hPG80 levels is both an independent prognostic marker in mRCC and also improves current clinical prognostic models. This will help stratify mRCC patients more accurately in future and improve the management of mRCC patients. Abstract Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients. Manish Kohli 1,*, Winston Tan 2, Bérengère Vire 3, Pierre Liaud 3, Mélina Blairvacq 3, Frederic Berthier 4, Daniel Rouison 4, George Garnier 4, Léa Payen 5, Thierry Cousin 6, Dominique Joubert 6 and Alexandre Prieur 6,* + Journals - Cancers - Volume 13 - Issue 3 - 10.3390/cancers13030375 The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients ​ Dec, 2019 EBiomedicine by THE LANCET déc. 2019 Authors : Benoit You Frédéric Mercier Eric Assenat Carole Langlois-Jacques Olivier Glehen Julien Soulé et al. In colorectal cancer, hPG80 (progastrin) is released from tumor cells, promotes cancer stem cells (CSC) self-renewal and is detected in the blood of patients. Because the gene GAST that encodes hPG80 is a target gene of oncogenic pathways that are activated in many tumor types, we hypothesized that hPG80 could be expressed by tumors from various origins other than colorectal cancers, be a drug target and be detectable in the blood of these patients. […] Research in context Evidence before study The National Cancer Institute recently highlighted the need forbiomarkers to improve early detection of cancers, monitor treatment effects and detect disease relapses. Therefore, the identification of a new tumor blood-based marker with broad expression across tumor types might have a significant impact on diagnostic and follow-up of patients. hPG80 (progastrin) was shown to be over-expressed in human colorectal tumor cells. Interestingly, GAST is a direct target of the Wnt/ß-catenin/Tcf4 oncogenic pathway. Since this pathway is activated inmany other cancers and plays a major function in cancer stem cells survival, we hypothesized that hPG80 (i) might be expressed by other types of cancers, and would be present in the blood of patients with tumors different from colorectal cancers and (ii) might be a drug target for various type of cancers. ​ Added value of this study Here we show that hPG80 is expressed by the tumor and present in the blood of 11 different types of cancer patients. Two retrospective kinetic studies where blood samples were collected regularly from cancer patients undergoing different treatments revealed strong associations between longitudinal hPG80 . ..... concentrations and anti-cancer treatment efficacy. We provide data showing the decrease of hPG80 after surgery in a cohort of patients with peritoneal involvements from gastroin-testinal cancers, treated with peri-operative chemotherapy regimens and cytoreductive surgery. We also show the correlationbetween hPG80 levels and standard imaging in a cohort of patients with hepatocellular carcinoma, managed with local or systemic treatments, including patients with no detectable levels of alpha-fetoprotein. Finally, we show that targeting hPG80 with our humanized antibody decreases self-renewal capacity of cancer stem cells from various origins. ​ Implications of all available evidence The technology we developed to detect hPG80 in the blood isr obust, reliable and inexpensive, making this test easy to implement by oncologists. This technology could be used to improve early cancer diagnosis and treatment efficacy monitoring. Furthermore, in this study we show that our anti-hPG80 therapeutic antibody, that was initially found to target the Wnt pathway and decrease self-renewal capacity in cancer stem cells from colorectal cancer, is envisioned to have the same effect on tumors from other origins. + Direct Comparison of Diagnostic Performance of 9 Quantitative Fecal Immunochemical Tests for Colorectal Cancer Screening ​ Sep, 2017 Gastroenterology, 2017 September Authors : Anton Gies1, Katarina Cuk2, Petra Schrotz-King1, Hermann Brenner A variety of fecal immunochemical tests (FITs) for hemoglobin (Hb) are used in colorectal cancer screening. It is unclear to what extent differences in reported sensitivities and specificities reflect true heterogeneity in test performance or differences in study populations or varying pre-analytical conditions. We directly compared the sensitivity and specificity values with which 9 quantitative (laboratory-based and point-of-care) FITs detected advanced neoplasms (AN) in a single colorectal cancer screening study. […] + Targeting the Wnt pathway and cancer stem cells with anti-progastrin humanized antibodies: a major breakthrough for K-RAS mutated colorectal cancer treatment Jun, 2017 Clinical Cancer Research, 2017 June Authors : Alexandre Prieur, Monica Cappellini, Guillaume Habif, Marie-Paule Lefranc, Thibault Mazard, Eric Morency, Jean-Marc Pascussi, .../... Chris Planque, Eric Assenat, Frédéric Bibeau, Jean-François Bourgaux, Pascal Pujol, Alain Sézeur, Marc Ychou and Dominique Joubert Patients with metastatic colorectal cancer (CRC) suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for[…] + Common pitfalls in preclinical cancer target validation ​ May, 2017 Nature reviews, 2017 May Authors : William G. Kaelin Jr An alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being misled by off-target effects when using pharmacological or genetic perturbants in complex biological assays. This danger is particularly acute when, as is often the case in cancer pharmacology, the biological phenotype being measured is a […] + Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. ​ Dec, 2016 JAMA Oncol. 2016 Dec 3. Authors : Global Burden of Disease Cancer Collaboration, Fitzmaurice, Allen, Barber, Barregard, Bhutta, Brenner, Dicker .../... Zaidi, Zaki, Zenebe, Murray, Naghavi. Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. […] + Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem-like Cells. ​ Jun, 2016 Cancer Res. 2016 June Authors : Giraud, Failla, Pascussi, Lagerqvist, Ollier, Finetti, Bertucci, Ya, Gasmi, Bourgaux, Prudhomme, Mazard, Ait-Arsa, Houhou, Birnbaum, Pélegrin, Vincent, Ryall, Joubert, Pannequin, Hollande. Subpopulations of cancer stem-like cells (CSC) are thought to drive tumor progression and posttreatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable proportions of self-renewing CSC within heterogeneous tumors under homeostatic conditions remain poorly understood. Progastrin is a secreted peptide that exhibits tumor-forming potential in colorectal cancer, where it regulates pathways known to modulate colon CSC behaviors. In this study, we investigated the role of progastrin in […] + The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies ​ Feb, 2016 Lab Invest. 2016 February Yang, Wang, Zhang, Wang, Nan, Li, Zhang, Mohammed, Haydon, Luu, Bi, He. he canonical WNT/β-catenin signaling pathway governs a myriad of biological processes underlying the development and maintenance of adult tissue homeostasis, including regulation of stem cell self-renewal, cell proliferation, differentiation, and apoptosis. WNTs are secreted lipid-modified glycoproteins that act as short-range ligands to activate receptor-mediated signaling pathways. The hallmark of the […] + Progastrin a new pro-angiogenic factor in colorectal cancer ​ Jun, 2015 Oncogene. 2015 June Authors : Najib S1, Kowalski-Chauvel A1, Do C1, Roche S2, Cohen-Jonathan-Moyal E3, Seva C1. Angiogenesis is essential in tumor progression and metastatic process, and increased angiogenesis has been associated with poor prognosis and relapse of colorectal cancer (CRC). VEGF has become the main target of anti-angiogenic therapy. However, most patients relapse after an initial response or present a resistance to the treatment. Identification of new pro-angiogenic factors may help to improve anti-angiogenic therapy. In this study, we demonstrated that the pro-hormone progastrin (PG), over-expressed in[…] + Novel roles of gastrin ​ Jul, 2014 J Physiol. 2014 Jul 15 Authors : Dimaline, Varro The existence of the hormone gastrin in the distal stomach (antrum) has been known for almost 110 years, and the physiological function of this amidated peptide in regulating gastric acid secretion via the CCK2 receptor is now well established. In this brief review we consider important additional roles of gastrin, including regulation of genes encoding proteins such as […] + Gastric secretion ​ Nov, 2013 Curr Opin Gastroenterol. 2013 Nov Authors : Shijian Chu;Mitchell Schubert; The review summarizes the past year's literature, basic science and clinical, regarding the neural, paracrine, hormonal, and intracellular regulation of gastric acid secretion.[…] + Wnt Signaling in Cancer ​ May, 2012 Cold Spring Harb Perspect Biol. 2012 May Authors : Paul Polakis Aberrant regulation of the Wnt signaling pathway is a prevalent theme in cancer biology. From the earliest observation that Wnt overexpression could lead to malignant transformation of mouse mammary tissue to the most recent genetic discoveries gleaned from tumor genome sequencing, the Wnt pathway continues to evolve as a central mechanism in cancer biology. This article summarizes the evidence supporting a role for Wnt signaling in human cancer. This includes a review of […] + The wnt target jagged-1 mediates the activation of notch signaling by progastrin in human colorectal cancer cells. ​ Aug, 2009 Cancer Res. 2009 August Authors : Julie Pannequin, Caroline Bonnans, Nathalie Delaunay, Joanne Ryan, Jean-François Bourgaux, Dominique Joubert and Frédéric Hollande The Wnt and Notch signaling pathways are both abnormally activated in colorectal cancer (CRC). We recently showed that progastrin depletion inhibited Wnt signaling and increased goblet cell differentiation of CRC cells. Here, we show that progastrin down-regulation restores the expression by CRC cells of the early secretory lineage marker Math-1/Hath-1 due to […] + Beta-catenin/Tcf-4 inhibition after progastrin targeting reduces growth and drives differentiation of intestinal tumors ​ Nov, 2007 Gastroenterology. 2007 Nov. Authors : Pannequin J1, Delaunay N, Buchert M, Surrel F, Bourgaux JF, Ryan J, Boireau S, Coelho J, Pélegrin A, Singh P, Shulkes A, Yim M, Baldwin GS, Pignodel C, Lambeau G, Jay P, Joubert D, Hollande F. Aberrant activation of the beta-catenin/Tcf-4 transcriptional complex represents an initiating event for colorectal carcinogenesis, shifting the balance from differentiation toward proliferation in colonic crypts. Here, we assessed whether endogenous progastrin, encoded by a target gene of this complex, was […] + Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis ​ Aug, 2000 J Clin Invest. 2000 August Authors : Theodore J. Koh,1 Clemens J. Bulitta,1 John V. Fleming,1 Graham J. Dockray,2 Andrea Varro,2 and Timothy C. Wang1 Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene occur in most colorectal cancers and lead to activation of β-catenin. Whereas several downstream targets of β-catenin have been identified (c-myc, cyclin D1, PPARδ), the precise functional significance of many of these targets has not been examined directly using genetic approaches. Previous studies have shown that […] + Expression but incomplete maturation of progastrin in colorectal carcinomas ​ Apr, 1993 Gastroenterology. 1993 April Authors : Van Solinge WW1, Nielsen FC, Friis-Hansen L, Falkmer UG, Rehfeld JF. To evaluate the hypothesis that gastrin is a local growth factor in colonic carcinomas, the expression of gastrin messenger RNA (mRNA) and peptides were examined in five human colon carcinoma cell lines, 12 solid colon carcinomas, and normal colonic tissue... […] + A synthesis of the knowledge of progastrin is available on the website of the Progastrin cancer control association. + Posters hPG80 Last Posters Poster Session : Prognostic value of circulating progastrin (hPG80) in IDH-wild type glioblastoma treated with radio-chemotherapy . Partnership Download the Poster https://meetings.asco.org/abstracts-presentations/208791 Poster Session : Plasma hPG80 (circulating progastrin) as a novel prognostic biomarker for hepatocellular carcinoma at early to intermediate stages (BCLC 0 to B) Partnership Download the Poster https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.4_suppl.472 Poster Session : HPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms. Partnership Download the Poster https://aacrjournals.org/cancerres/article/81/13_Supplement/735/669496/Abstract-735-hPG80-circulating-progastrin-a-novel #GI ASCO 2020 628 Poster Session (Board #G9 ) : HPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms. Partnership Download the Poster https://www.carcinoid.org/wp-content/uploads/2020/02/Progastrin-Biomarker-for-Detection-of-Neuroendocrine-Neoplasms.pdf 3037 / 29 - Progastrin, a novel ubiquitous cancer blood biomarker for early detection and monitoring. Partnership Download the Poster https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.3037 2289 / 18 - Prognostic impact of progastrin levels in blood compared to MSKCC based clinical prognosis in metastatic renal cell cancer patients Partnership Download the Poster https://www.abstractsonline.com/pp8/#!/6812/presentation/4883 2294 / 23 - Plasma progastrin level as a predictive and prognostic biomarker in advanced prostate cancer Partnership Download the Poster https://www.abstractsonline.com/pp8/#!/6812/presentation/4888 2222 / 11 - Progastrin a new biomarker for hepatocellular cancer patient follow-up Partnership Download the Poster https://www.abstractsonline.com/pp8/#!/6812/presentation/5077 119P - Progastrin, a new blood biomarker for the diagnostic and therapeutic monitoring, in gastro-intestinal cancers: A BIG-RENAPE project. Partnership Download the Poster https://academic.oup.com/annonc/article/29/suppl_8/mdy269.117/5141327