A chemo-genetic approach to identify novel anti-cancer compounds and drug targets related to the TOR pathway

• Research unit: INNOSUISSE
• Project number: 9417.1;8 PFLS-LS

Short description (English)

A chemo-genetic approach to identify novel anti-cancer compounds and drug targets related to the TOR pathway

Abstract (English)

Mammalian Target of Rapamycin (mTOR) is a protein with protein kinase activity which integrates growth stimulatory and oxygen-, nutrient- and energy-sensing pathways. As the signaling molecules controling mTOR are altered in many human cancers, the mTOR pathway offers several attractive targets for treatment. In a previous still ongoing 11-month KTI project, we have successfully isolated several classes of mTOR inhibitors by using an isogenic cellular system designed to identify TOR-pathway inhibitors developed in the laboratory of the main applicant. In the present application we propose in part A to characterize the mode of action of the identified classes and translate the findings from murine to human cancer cells. In part B, we shall perform a genomic screen using a lentiviral genomic shRNA library to identify from cells with TOR-pathway activation candidate drug targets related to the TOR-pathway. They will be tested for reactivity with the identified Actelion compounds, and some developed further into novel drug screening systems. Compounds identified by the proposed strategy might be relevant for the treatment of cancer, but also for other conditions such as metabolic disorders, diabetes, cardiovascular disease and longevity, where the TOR-pathway has been implicated.