Converting Mutant p53 into an Actionable Target for the Treatment of Ovarian Cancer
Abstract
The recent addition of bevacizumab to the treatment of primary ovarian cancer and its FDA approval for this disease follow from the AURELIA and GOG/NRG 218 trials. From 1873 enrolled patients on GOG/NRG 218, it was found that the addition of bevacizumab to chemotherapy and its inclusion in the extended period resulted in a significant improvement in progression free survival (PFS) of 4 months compared to chemotherapy alone, with a hazard ratio of 0.717. The critical questions that must now be answered are 1) what are the molecular markers that predict for response on this landmark ovarian cancer trial? and 2) what are alternative treatment strategies for non-responders? Our central hypothesis is that targeted agents including bevacizumab, chosen based upon the knowledge of the TP53 mutational status, synergize with chemotherapy and/or the PARP inhibitor olaparib and promote catastrophic tumor cell death. These studies are anticipated to have a significant positive impact on the field by enhancing the design and choice of therapy for ovarian cancer based on TP53 mutations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1193689
Entities
People
- Kimberly K Leslie
Organizations
- University of New Mexico