Dr. Landen Discusses p53 Mutations in Ovarian Cancer

Chip Landen, MD, associate professor, Division of Gynecologic Oncology, University of Virginia Health System, discusses the role of p53 mutations in patients with ovarian cancer.

Investigators have known for quite a long time that p53 is the most common mutation in ovarian cancer, Landen says. About two-thirds of p53 are what are known as missense mutations, where the majority of the protein is still made and functionable. In fact, that function may be more oncogenic and act as a tumor driver rather than a tumor suppressor.

About one-third of patients have null mutations, adds Landen; this means that the p53 gene is not made or expressed in their tumors. Because missense mutations change the functionality of the cell, it allows the tumor to grow more efficiently. Small molecule inhibitors targeting p53 have been developed in an attempt to change how the proteins are folded. How they are folded, Landen notes, is a critical factor in how the proteins will function. These emerging agents have shown promise in preclinical models and are being evaluated in phase II trials now.