Neil Johnson, PhD
Fox Chase Cancer Center
Investigating the ability of splicing inhibitors to target BRCA1 mutant ovarian cancer
Though patients with mutations in the BRCA1 gene respond better to cisplatin and PARP inhibitors than patients without mutations, resistance to these drugs remains a major obstacle for the successful long-term treatment of ovarian cancer. Dr. Johnson’s group recently showed that cancer cells with certain BRCA1 mutations are able to produce an alternative version of the BRCA1 protein that makes them resistant to PARP inhibitors and cisplatin. This phenomenon likely applies to almost 30% of all known mutations in the BRCA1 gene. Cells rely on a protein complex called the splicesome to make this version of BRCA1. Dr. Johnson wants to use drugs, known as splicesome inhibitors to block the function of the splicesome and prevent this resistance-causing variant from being produced with the aim of preventing the associated drug resistance. If successful, splicesome inhibitors may provide the means to combat resistance in a subset of patients with BRCA1 mutations.