Professeur Alexandre de la Taille
Equipe n° :07 CSS n° : 4 Unité :955
The INSERM U955Eq07 team is a strong association of clinicians, oncologists, pathologists, biochemistrists and basic researchers in a dedicated environment that allows high scientific level facilities working on prostate and bladder cancers. The goal is to determine the most relevant molecular events, to define the molecular risk factors associated with therapy success and resistance and to identify new therapeutic targets. During the past 5 years, the group worked on identifying biomarkers to try to reduce overdiagnosis and personalized therapeutic approaches in prostate cancer such as urine PCA3, serum testosterone, betaTUBIII, protocadherin PC, androgen receptor and telomerase instability and molecular pathways PI3K/Akt, Wnt (Wnt / β-catenin). An inhibitor of nucleophosmin N6L was also evaluated. Hormonal environment was also evaluated in Caucasian and Caribbean patients and highlighted that estrone and estrone sulfate levels were correlated with aggression. The team identified FSH receptor on the surface of endothelial cells that correlates with tumor behavior. In bladder cancer, FGFR3 mutations correlated with superficial cancers was validated and loss of CDKN2A expression was found to be associated with aggressiveness. Two programs for Excellence in bladder cancer were started: CIT has shown the association between cancer and the presence of aggressive T2 MRES phenotype (Regional Multiple Epigenetic Silencing) and characterization of a subset of T2 with an addiction to EGFR pathway and the FP7 program involving DECaNBio with Spain in 1070 patients with bladder cancer to explore by SRM of aggressiveness and recurrence of low-grade cancer markers.
The next projects on prostate cancer are to continue to investigate biomarkers of lethal prostate cancer using high-throughput microarray technologies (PAIR Prostate), to validate new prostate cancer treatments such as mdv3100, orteronel or abiraterone and to find molecular pathways involved in resistance on preclinical models, to study regulations of cancer cell proliferation and invasion by Heparin-affin regulatory growth factor (HARP) and to determine hormonal profiles of prostate cancer patients. For bladder cancer, our group will develop the molecular taxonomy of bladder cancer and continue to validate new prognostic factors.
5 best publications:
Allory, Y.; Beukers, W.; Sagrera, A.; Flandez, M.; Marques, M.; Marquez, M.; van der Keur, K.A.; Dyrskjot, L.; Lurkin, I.; Vermeij, M.; Carrato, A.; Lloreta, J.; Lorente, J.A.; Carrillo-de Santa Pau, E.; Masius, R.G.; Kogevinas, M.; Steyerberg, E.W.; van Tilborg, A.A.; Abas, C.; Orntoft, T.F.; Zuiverloon, T.C.; Malats, N.; Zwarthoff, E.C.; Real, F.X. Telomerase Reverse Transcriptase Promoter Mutations in Bladder Cancer: High Frequency Across Stages, Detection in Urine, and Lack of Association with Outcome. European urology 2013.
Cross Modulation between the Androgen Receptor Axis and Protocadherin-PC in Mediating Neuroendocrine Transdifferentiation and Therapeutic Resistance of Prostate Cancer. Terry S, Maillé P, Baaddi H, Kheuang L, Soyeux P, Nicolaiew N, Ceraline J, Firlej V, Beltran H, Allory Y, de la Taille A, Vacherot F. Neoplasia. 2013 Jul;15(7):761-72.
Androgens regulate Hedgehog signalling and proliferation in androgen-dependent prostate cells.Sirab N, Terry S, Giton F, Caradec J, Chimingqi M, Moutereau S, Vacherot F, de la Taille, Kouyoumdjian JC, Loric S. Int J Cancer. 2012 Sep 15;131(6):1297-306.
Class III beta-tubulin expression predicts prostate tumor aggressiveness and patient response to docetaxel-based chemotherapy. Ploussard G, Terry S, Maillé P, Allory Y, Sirab N, Kheuang L, Soyeux P, Nicolaiew N, Coppolani E, Paule B, Salomon L, Culine S, Buttyan R, Vacherot F, de la Taille A. Cancer Res. 2010 Nov 15;70(22):9253-64.
Expression of follicule-stimulating hormone receptor in tumor blood vessels. Radu A, Pichon C, Camparo P, Antoine M, Allory Y, Couvelard A, Fromont G, Hai MT, Ghinea N. N Engl J Med. 2010 Oct 21;363(17):1621-30.
Ce groupe a pour objectif de développer les techniques d’ingénierie tissulaire et de thérapies cellulaires pour la chirurgie fonctionnelle et de reconstruction de l’appareil urinaire. In évalue également les nouvelles techniques de simulation et de robotique chirurgicale.