SPORE in Ovarian Cancer

Ovarian cancer is one of the most aggressive cancers in the United States and a major cause of cancer morbidity and mortality. This Johns Hopkins-University of Pennsylvania Ovarian Cancer SPORE application focuses on reducing ovarian cancer incidence and mortality by translating new laboratory-based discoveries into improvements in ovarian cancer diagnosis and treatment. This highly translational program contains three hypothesis-driven Research Projects, three Core Resources, the Career Enhancement Program (CEP), and the Developmental Research Program (DRP). The objective of Project 1 is to develop a novel brush-based approach to sample fallopian tubes and ovaries for precursor lesions and to define the molecular attributes of detected precursors for proper clinical management. The goal of Project 2 and Project 3 is to provide critical preclinical and early clinical data for developing more effective combined therapy to treat advanced ovarian cancer, especially for recurrent diseases. Specifically, Project 2 will evaluate cyclin E1 protein as a biomarker of ovarian cancers responsive to a new WEE1 inhibitor. Resistance will be addressed with combination WEE1 and ATR inhibition and underlying mechanism of response and resistance will be defined by treatment-related proteins identified at stressed replication forks. Project 3 will exploit a DNA repair vulnerability in ARID1A mutant ovarian cancers. Specifically, the clinical efficacy of the combination of temozolomide and the PARP inhibitor, senaparib, will be evaluated in a Phase II trial. All the three new projects originate from the current CEP/DPR projects. These Projects are supported by an Administrative Core, a Biorepository/Pathology Core, and a Computation/Biostatistics Core. Finally, the CEP and DRP comprise pipelines of human capital and innovative ideas, respectively, which will fuel future SPORE advances. This application is strongly supported by institutional commitment to ensure its success.