2. Cell reprogramming and therapeutic resistance

2. Signaling rewiring and molecular mechanisms in acquired endocrine resistanceThe initial existence or posterior development of resistance to one or several anti-cancer treatments is certainly the most frequent cause of failure to cure of cancer patients. Despite major advances in understanding of the molecular basis of cancer obtained during recent years, there are very few examples of the translation of therapeutic strategies against resistance. This limitation is largely due to the lack of "integrated" models of resistance to the various standard drugs.

acWe have generated a collection of ortho-xenograft tumors in nude mice that are used for the study of the genetics of chemoresistance. Familial cases, and ER-negative and triple-negative primary or post-treatment tumors are engrafted in nuce mice and, subsequently, evaluated for their response in vivo to several compounds/drugs. The relapsing tumors are processed for exome sequencing and acquired mutations analysed in the original tissue sample and/or original xeonograft. Findings are validated prospectively.