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 nonresponders? Our central hypothesis is that targeted agents including bevacizumab, chosen based upon the knowledge of the TP53 mutational status, synergize with chemotherapy 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 specific TP53 mutations.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2021
Accession Number
AD1166356

Entities

People

  • Kimberly K Leslie

Organizations

  • University of Iowa

Tags

DTIC Thesaurus Topics

  • Biological Factors
  • Carcinoma
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Colon Cancer
  • Enzyme Inhibitors
  • Gene Expression
  • Genetics
  • Health Services
  • Medical Personnel
  • Molecular Dynamics
  • Oncology
  • Peptides
  • Proteins
  • Statistical Analysis

Readers

  • Oncology
  • Systems Analysis and Design