Chip Landen, MD, associate professor, Division of Gynecologic Oncology, University of Virginia Health System, discusses the role of 

 mutations in patients with ovarian cancer.

Investigators have known for quite a long time that 

 is the most common mutation in ovarian cancer, Landen says. About two-thirds of 

 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 

 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 

 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.

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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.

Dr. Landen Discusses p53 Mutations in Ovarian Cancer

Chip Landen, MD, associate professor, Division of Gynecologic Oncology, University of Virginia Health System, discusses the molecular subtypes of ovarian cancer.

It is important for community oncologists to understand that there are multiple subtypes of ovarian cancer. There are 2 main subtypes: epithelial and serous—the latter being the most common, Landen says. Essentially of those histologies have 

 mutations that develop early in the oncogenic process, resulting in several different genetic changes in the disease history.

Other than that, in terms of number of tumor mutations, ovarian cancer in general falls into the “moderate” category compared with other tumor types. There are very few individual genes that are frequently mutated in the majority of patients, Landen adds. 

 are the most common genetic alterations, although they are usually germline mutations. About 7% of ovarian cancers have 

 mutations that are somatic, meaning they occur in the tumor rather than having been inherited.

Chip Landen, MD

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Dr. Landen Discusses p53 Mutations in Ovarian Cancer

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