In vitro modeling and genotype-specific therapeutic targeting of DNA repair deficient prostate cancer (Dr. med. Dilara Akhoundova, Medical Oncologist)
Genomic profiling-based personalized treatment of metastatic PCa (mPCa) is a rapidly emerging field of precision oncology. Alterations in DNA damage repair (DDR) genes are present in up to 25% of advanced PCas, more than half of which are found in non-BRCA DDR genes. While inhibitors of poly-ADP-ribose polymerase (PARPis) have demonstrated clinical efficacy in tumors with BRCA1, BRCA2, and a subset of tumors with PALB2 and ATM alterations, highly heterogeneous responses are observed for other non-BRCA DDR alterations. Within this project, we aim to establish and functionally characterize novel in vitro models of non-BRCA PCa DDR deficiency by generating isogenic PCa cell lines deficient for ATM, FANCA and CHEK2. The overall goal of this project is to uncover genotype-specific therapeutic vulnerabilities for ATM, FANCA- and CHEK2-deficient PCa, which currently lack successful molecularly targeted treatment options. Moreover, this project aims to characterize the clinical features and molecular landscape of a unique Swiss cohort of patients with non-BRCA DDR-altered PCas.
The project is supported by the Nuovo-Soldati Foundation for Cancer Research and Kurt und Senta Hermann Foundation.
