First-in-class FA/BRCA pathway inhibitors for cancer therapeutics
Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Tumors have the ability to develop resistance to traditional treatments. This project proposes an innovative approach to target cancer with a new DNA damage repair inhibitor. The DNA damage repair pathway has already been explored in cancer therapeutics through the successful use of new PARP inhibitors in tumors with mutations in BRCA genes.
Cancer is a leading cause of death worldwide, accounting for an estimated 9.6 million deaths in 2018. Targeted therapy in oncology is becoming increasingly important and necessary, as tumors frequently become resistant to conventional treatments, the main cause of cancer deaths.
Among targeted therapy approaches, DNA damage repair has become a hot topic in recent years. Approval of PARP inhibitors to treat different cancers with mutations in BRCA genes has dramatically improved survival of these highly resistant cancers.
Thanks to their deep knowledge of the FA/BRCA pathway Jordi Minguillón and team have identified a novel target (a specific protein-protein interaction) and the first-in-class small molecules able to inhibit this pathway. After several steps of target identification, hit identification, hit validation and medicinal chemistry, they are now in the hit optimization steps of their molecule candidates. The potential applications of FANCONINIB include synthetic lethality, synergy with tumor immunotherapy, and chemosensitization of conventional chemotherapy, in specific tumors.