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Localized prostate cancer: a molecular signature to identify non-aggressive tumours

Although prostate cancer is the most frequent cancer in men, only 15% of patients will eventually develop a metastatic disease. However, immediate radical surgery (prostatectomy) remains a standard of care for localized prostate tumours, and may lead to many complications impacting patient’s quality of life. Actual clinical and molecular tools do not accurately identify patients with non-evolutive/indolent tumours. A CIT study carried out in collaboration with Professor O.Cussenot, Head of the Urology Department at Paris Est University Hospital, led to the identification of a molecular subtype of tumours accounting for 20% of patients with localized prostate cancer and highly predictive of a non-evolutive disease. This work also provides a set of robust biomarkers as a clinical diagnostic tool to accurately identify these tumours. Using this molecular subtyping, active surveillance could be systematically proposed as a standard of care to 1 over 5 patients with localized prostate cancer, therefore saving them from radical surgery.

Kamoun, A., Cancel-Tassin, G., Fromont, G., Elarouci, N., Armenoult, L., Ayadi, M., Irani, J., Leroy, X., Villers, A., Fournier, G., et al. (2018). Comprehensive molecular classification of localized prostate adenocarcinoma reveals a tumour subtype predictive of a non-aggressive disease. Ann. Oncol.

Immune Environnement Impacts the Prognosis of Colon Tumors

Research conducted in collaboration with Alex Duval’s team (Inserm UMRS 938, Saint-Antoine Hospital Research Center, Paris) allowed us to better assess the impact of the tumor microenvironment on the prognosis of colorectal tumors. This work also may explain why certain immunotherapies are effective in a particular population of patients with colorectal cancer.

The tumors contain both tumor cells and non-tumor cells. The latter form the “tumor microenvironment”. The cells of the microenvironment can have a major effect on the evolution of the cancerous disease. For example, it is well known that a strong lymphocyte infiltration, typical of tumors with microsatellite instability (MSI), is a factor of good prognosis in colorectal tumors. Interestingly, metastatic MSI tumors respond very well to immunotherapies designed to activate the immune response of patients by releasing T-cell activity (called immune checkpoint-based therapies). Based on this observation, we studied the microenvironment of colorectal tumors, aiming to evaluate the quality of the antitumour immune response in an extremely comprehensive manner. Our results have shown that, within metastatic MSI tumors, the antitumour immune response can not develop because of a very strong expression of factors inactivating T lymphocytes, which are nevertheless present in a large quantity. In the end, the method developed makes it possible to obtain prognostic information that is more accurate than the sole analysis of lymphocyte infiltration. In the future, it may also be particularly useful in guiding the use of immunotherapy based on immune checkpoint inhibitors in the treatment of colorectal cancer.

L. Marisa, M. Svrcek, A. Collura, et al., The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors. JNCI, 2017. PMID: 28922790

Our work on the validation of the clinical utility of the molecular classification of colorectal cancers will be presented at the ASCO meeting on June 6

IDJ_20170531_CITatAsco2017
After the development of a molecular classification of colorectal cancers internationally accepted, the CIT team is developing a diagnostic and predictive tool to improve the care of patients suffering from these cancers. The first results on the validation of this tool will be presented at the International Congress of the American Association of Clinical Oncology (ASCO), which will take place in Chicago from 2 to 6 June 2017. The ASCO meeting is the most important world congress dedicated to clinical oncology.

The CIT team, in collaboration with the team of Pierre Laurent-Puig, a gastroenterologist at the Georges Pompidou European Hospital in Paris (Inserm UMR-S775, Paris), is developing a tool for the clinical use of the molecular classification of colorectal cancers (1, 2). The utility of this tool for the diagnosis and the prediction of the response to treatment is the object of validation studies carried out on large cohorts of patients. A first study was performed on a cohort of more than 1,700 patients, with or without the targeted treatment Cetuximab, the PETACC-8 clinical trial sponsored by the French Federation of Digestive Cancer (FFCD). The first results of this work have been selected for oral presentation at the ASCO 2017 meeting. This presentation will take place on the morning of Tuesday 6 June at the Clinical Science Symposium: Making Sense of Consensus Molecular subtypes. With nearly 30,000 participants, the ASCO meeting is the opportunity of major announcements for the evolution of clinical practices in oncology.

(1) L. Marisa et al., 2013, Plos Medicine
(2) J. Guinney et al., 2015, Nature Medicine
(3) ASCO, American Society of Clinical Oncology, Annual Meeting 2017