Académie royale de Médecine de Belgique


Résumé de Fred Sauvage (Séance du 21 octobre 2006)


par F. de SAUVAGE (Genentech Inc.), invité.

Combination of agents targeting signaling pathways involved in tumor cell proliferation and survival, apoptosis, angiogenesis or other communication with the microenvironement offers the most promising avenue for the treatment of cancer. I will describe our efforts to identify new targets in several of these areas and in particular will discuss our progress in targeting the Hedgehog (Hh) pathway, an ancient signaling cascade that is crucial for proper development but remains relatively quiet in adult life.  However, aberrant reactivation of the pathway in adult tissue can lead to the development of cancer.  Hh pathway activation in tumors such as basal cell carcinoma and meduloblastoma is the result of inactivating mutations in PATCHED (PTCH) or activating SMOOTHENED (SMO) mutations. However, Hh pathway activation in other tumors, such as small cell lung, pancreatic or prostate cancer is the result of upregulation of ligand expression in the tumor cells, which may act in an autocrine or paracrine manner. Targeting the Hh pathway with small molecule antagonists of the pathway therefore provides a new therapeutic opportunity for the treatment of both tumor types.