The treatment of cancer has been transformed by therapies that specifically target mutated drivers of tumor growth, survival, and resistance. Many of these treatments have fewer toxic side effects as compared to traditional chemotherapy and have demonstrated dramatic response rates, improved times to progression, and prolonged survival. For example, enzalutamide, a drug that targets the androgen receptor in hormone-refractory prostate cancer, has had a major impact on the survival rates for late-stage castration-resistant disease. As shown on the graph to the right, however, most patients eventually progress within two years. Unfortunately, upon enzalutamide relapse those patients lack further treatment options. Despite these therapeutic advances, an estimated 27,540 men will die of their disease in 2015, primarily due to the development of resistance to therapy.
ORIC’s drug discovery vision integrates the identification of new, molecularly defined pathways of resistance with clinic-based phenotypic validation. A rigorous understanding of the molecular and genetic adaptations by cancers to various targeted therapies underpins the novel treatments ORIC seeks to develop. This is possible because recent technological advances have allowed for the detailed analysis of the genetic landscape of patient tumor samples. Drawing upon the expertise of its scientific founders, ORIC has implemented approaches to identify novel mechanisms of resistance. These efforts will result both in the identification of novel targets for therapy as well as biomarkers to define the patient subsets for whom the therapy would be most efficacious. ORIC’s scientists have already prioritized several potential therapeutic targets and accomplished extensive optimization towards ultimately choosing development candidates for clinical testing in relapsed-refractory cancer patients.