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  • Home | hPG80 - A major target against Cancer | ECS Progastrin

    Last updated: August 3, 2020 HOWEVER The real battle against cancer is fought by physicians and patients! Our mission is simply to provide healthcare professionals with innovative tools that are the most reliable and effective possible. The hPG 80 blood biomarker has now been shown to be both a major weak point of cancer and a fundamental target to providing physicians with multiple solutions, now and in the future * : In cancer, hPG 80 is overexpressed in the tumor and detectable in the patient’s blood [1] . 16 different cancers have been tested, the 16 were positive. Of these 16 cancers, 11 have been published to date [1] . ​ Cancer stem cells express elevated levels of hPG 80 (circulating progastrin) [2][3] . Secretion of hPG 80 maintain tumor-initiating and self-renewal capabilities of cancer stem cells [3] . hPG 80 is released from the tumor and becomes detectable in the blood across all stages [3][4] . Plasma hPG 80 is elevated in a wide range of cancer patients [5] hPG 80 is produced by all cancer cells, but in quantities 100 to 1000 times higher by cancer stem cells [2] , making hPG 80 the only blood biomarker that gives information on tumor activity. BIBLIOGRAPHY [1]. You et al, EBioMedicine, 2020 Jan;51:102574 [2]. Giraud et al, Cancer Res, 2016;76(12):3618-28 [3]. Siddheshwar et al, Gut, 2001 Jan; 48(1): 47–52 [4]. Prieur et al, Clin Cancer Res. 2017;23(17):5267–5280 [5]. Konieczkowski et al, Cancer Cell, 2018 May 14;33(5):801-815 KEY FACTS CURRENT AND PROSPECTIVE CLINICAL APPLICATIONS CURRENT FOLLOW UP hPG 80 measurement, and its trend, from simple blood samples, can help Physicians in the follow-up of patients, providing them with additional meaningful information on: treatment efficacy , risk of minimal residual disease, risk of relapse. CURRENT DIAGNOSIS The presence or absence of hPG 80 in blood can also provide Physicians with an additional indicator of vigilance for earlier diagnosis , especially for at-risk populations and for cancers for which no biomarker exists . PROSPECTIVE OTHER USES In addition, other potential uses for hPG 80 are being investigated and will be available to physicians in a few years: hPG 80 neutralization has shown that it can lead to a new clinical approach to tumor reversion therapy that causes cancer cells to return to “normal”, hPG 80 can provide a major breakthrough in tumor localization by PET Scan imaging, Finally, the robustness of its detection in blood makes it possible to envisage in the short term the production of a hPG 80 rapid test providing physicians and health authorities with a new affordable and very minimally invasive tool that could help them in their early detection strategies. NOW AVAILABLE TO PHYSICIANS A NEW TOOL : The blood test for detection and measurement of the target hPG80 Learn more... AVAILABLE ONLY ON MEDICAL PRESCRIPTION Contact Us Medical Doctor / Docteur en médecine Medical Professor / Professeur en médecine Mr. / M Ms. / Mme I fully read and agree to the privacy policy. / J'ai lu et j'accepte les clauses de confidentialité. Send / Envoyer Thank you for your message / Merci pour votre message

  • Press Corner | hPG80 | Cancer | DxPG80 | ECS Progastrin

    Press Corner PRESS ENQUIRIES ➜ Contact us via e-mail Subscription Welcome to our press mailing list OUR HISTORY ➜ From the lab to the patient Last updated: August 3, 2020 PHOTOS & LOGOS PHOTOS & LOGOS VIDEOS VIDEOS PRESS RELEASES Jun 8 2 min hPG80 at ASCO 2021 - Prolevcan study Plasma hPG80 circulating prograstin levels in cancer patients in Nigeria: Prolevcan study Jun 8 3 min hPG80 at ASCO 2021 - Hepatocellular carcinoma ASCO Poster Session: Prognostic value of plasma hPG80, alone or in combination with AFP, in patients with hepatocellular carcinoma PRESS RELEASES PRESS RELEASES VIDEOS VIDEOS PHOTOS & LOGOS Icone Logo format: Illustrator picture Logo_Puce 2020.ai PHOTOS & LOGOS PHOTOS & LOGOS VIDEOS PRESS RELEASES PRESS RELEASES Dominique Joubert Presentation Video length : 2:30' French (English subtitle) Royalty-free video on demand ​ From the lab to the patient Performing a scientific demonstration and bringing it to the patient is the dream of every scientist that Dominique Joubert is living. The scientific demonstration in question here is a major precision: to be able to detect cancer and to reverse the tumour process, in other words, to "bring back to normal cells that were cancerous" . Our Montpellier laboratory Video length : 1:01' Video without audio royalty-free video on demand ​ ​ Lyon CHU laboratory Video length : 3:06' Video without audio royalty-free video on demand ​ ​ It's time to control cancer Contact us Send Your message has been sent.

  • hPG80 | Main Scientific Publications | ECS progastrin

    Publications Last Posters hPG80 Main Scientific Publications Last updated: Jully 2, 2021 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. . + 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

  • News | hPG80 | Cancer | DxPG80 | ECS Progastrin

    News Last updated: August 3, 2020 Jun 8 2 min hPG80 at ASCO 2021 - Prolevcan study Plasma hPG80 circulating prograstin levels in cancer patients in Nigeria: Prolevcan study Jun 8 3 min hPG80 at ASCO 2021 - Hepatocellular carcinoma ASCO Poster Session: Prognostic value of plasma hPG80, alone or in combination with AFP, in patients with hepatocellular carcinoma Apr 21, 2020 2 min A Major Publication: The Overexpression of hPG80 (circulating progastrin) in Multiple Cancers The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients Apr 21, 2020 1 min Dr. Aman Chauhan MD (Markey Cancer Center) speaking about hPG80 at #GI ASCO 2020 HPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms. GI ASCO / Presented Friday, January 24, 2020

  • Clinical Steering Committee | ECS progastrin

    Steering Committee Last updated: August 3, 2020 Pr. Benoit You Oncology Medical, Hospices Civils de Lyon, France - Chairman Academic medical oncologist working in Lyon University Hospital, France. He is the head of the early phase trial unit (CITOHL) and of the transversal research platform of Lyon University Hospital. He is specialized in drug development, clinical trials, pharmacokinetics, mathematical modeling of serum tumor markers kinetics, and gynecology/breast cancers. He is a member of the scientific committee of the collaborative group GINECO. He is the head developer of the website biomarker-kinetics.org meant to characterize the kinetics of circulating tumor markers. He is the coauthor of 232 Pubmed indexed articles. Pr. Marc Ychou Oncology Medical, Cancer Institut of Montpellier, France - Expert member Doctor specialist of digestive oncology. He’s the general director of the Montpellier Cancer Institut since 2016. He has been the director of the Canceropôle Grand Sud-Ouest and was the president of the digestive cancer group at Unicancer. He created and is leading the INSERM team "Integrated research for personalized medicine in digestive oncology" since 2015. He’s the author of 190 publications referenced on Pubmed about digestive oncology. He’s member of various organizations such as ASCO or SFC. Dr. Raju Pilai Oncology Medical, City Of Hope, USA - Expert Member hematopathologist at City of Hope. His current research studies focus on multi-dimensional genomic analysis of cancer, targeted therapy and immunotherapy. Triple board-certified in anatomic and clinical pathology, molecular genetic pathology and hematopathology, he is an active member of multiple professional associations, and has published more than 28 peer-reviewed publications, abstracts and book chapters. Pr. Céleste Lebbé Dermatology, Saint Louis Hospital, France - Expert Member Professor of Dermatology in Saint-Louis Hospital in Paris, and is currently Head of the Skin Cancer Unit in the Department of Dermatology. She has expertise both in terms of clinical and biological research melanoma and in virus-induced cancers and has been an investigator for more than 20 years in clinical trials in the field of dermato-oncology. She currently conducts biological research in the development of new melanoma models. She leads Melbase, a national biobank dedicated to advanced melanoma. Dr. Manish Kohli GU Oncology, Moffitt Cancer Center, USA - Expert Member Vice Chair of the Department of Genito-Urinary Oncology at Moffitt Cancer Center. Dr. Kohli is currently Co-Principal Investigator on multiple NIH R01 grant awards that are investigating cell-free nucleic acid-based biomarkers in advanced prostate cancer and the application of nano technology sciences to clinical medicine. Dr. Kohli’s research interests aim to fuse the power of tumor genomics with emerging sciences such as nanotechnology, using biomarkers to determine the most effective treatment strategy. Pr. Federico Cappuzzo Oncology Medical, AUSL della Romagna-Ravenna, Italia - Expert Member the Director of Medical Oncology and the Director of the Hematology and Oncology Department at AUSL della Romagna-Ravenna. He is member of several associations such as AIOM, ESMO, ASCO or IASCL. He’s member of the editorial board of Lung Cancer and the Chairman of the Educational Committee of IASLC. In 2006, 2009 and 2012 Dr Cappuzzo received research grants from AIRC on targeted therapies for lung cancer. He is the author of more than 200 papers in peer-review journals, mainly in translational research in lung cancer. Dr. Philippe Bedard Oncology Medical, Princess Margaret Cancer Center, Canada - Expert Member Associate Professor of Medicine at the University of Toronto. He’s part of the Medical Oncologist team in the Division of Medical Oncology. He is also the Fellowship Director for the Bras Drug Development Program at the Princess Margaret Cancer Centre in Toronto. In 2012 he received the Career Development Award by the Conquer Cancer Foundation of the American Society of Clinical Oncology and in 2017 he received the William E. Rawls Prize from the Canadian Cancer Society. He is the principal investigator for a number of ongoing phase I/II clinical trials in breast cancer and other advanced solid malignancies.

  • hPG80 | Main Scientific Publications | ECS progastrin

    Publications Last Posters hPG80 Main Scientific Publications Last updated: May 11, 2020 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. […] + 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 .../... 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. […] + 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 L ab 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. + hPG80 Last Posters Poster Session : HPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms. Partnership Download the Poster ... #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

  • hPG80 | Quick Facts | ECS Progastrin

    What is hPG 80 ? hPG 80 in Cancer Evolution Involvement of the Wnt pathway in tumorigenesis hPG 80, the biomarker of tumoral activity ​ Learn more about performances of hPG 80 hPG 80 A New Blood Biomarker to Help Monitoring Tumor Activity for Multiple Cancers Last updated: August 3, 2020 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 hPG80 (circulating progastrin) is detected in the blood of cancer patients. 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. 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. 2 hPG80 in cancer evolution The biomarker hPG 80 is present in the tumor / bloodstream of cancer patients at all stages of tumor progression, from primary tumor to metastasis. Example of CRC 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 hPG 80 and secretion of hPG 80 . Tumor Cell: always ON 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 hPG 80 for their survival (Giraud et al, Cancer Research, 2016; Prieur et al, Clin Cancer Research, 2017). ​ CSCs secrete 100 to 1000 more of hPG 80 than non-CSC cancer cells (Prieur et al, Clin Cancer Research, 2017). Secreted hPG 80 maintains the stemness of CSCs (Prieur et al, Clin Cancer Research, 2017). ​ Neutralization of secreted hPG 80 by a therapeutic antibody decreases CSCs frequency, metastatic seeding, increases chemosensitivity and delays relapses (Prieur et al, Clin Cancer Research, 2017). L earn more... about hPG 80 Performances

  • Home | ECS progastrin

    Last Update : Feb 02, 2020 News: Events Apr 21, 2020 1 min ASCO 2020 [May29 > Jun02] #ASCO20: We will present you the lastest results from work with our partners on the usefulness of targeting hPG80 for multiple cancers ! Apr 21, 2020 2 min A Major Publication: The Overexpression of hPG80 (circulating progastrin) in Multiple Cancers The technology we developed to detect hPG80 in the blood is robust, reliable and inexpensive, making this test easy to implement by onco... Apr 21, 2020 1 min Dr. Aman Chauhan MD (Markey Cancer Center) speaking about hPG80 at #GI ASCO 2020 HPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms. GI ASCO / Presented Friday, January 24, 2020

  • DxPG80 | IVD test for hPG80 measurement | ECS progastrin

    ​ DxPG 80 IVD ELISA Human circulating Progastrin (hPG80) Immunoassay ​ ​ ​ Last updated: September 26, 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, 1.0 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:

  • Privacy | hPG80 - A major target against Cancer | ECS Progastrin

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