Dr. Memarzadeh on p53 Reactivation in Ovarian Cancer

Sanaz Memarzadeh, MD, PhD, gynecologic oncologist, professor of obstetrics and gynecology, University of California, Los Angeles, discusses p53 reactivation in the treatment of patients with ovarian cancer.

There are 3 approaches that are being taken to restore p53 function. Many of these approaches are focused on restoring p53 folding, Memarzadeh says. It has to be a tetramer and properly folded, so that it can bind to DNA. APR-246 is 1 of the first drugs being tested. The drug was found in a drug screen specifically targeting cells that carry a type of p53 mutation. The compound, states Memarzadeh, has to be converted to methylene quinuclidinone. It then binds to cystines in either p53 or any molecule that carries a cystine. By doing so, it is thought to restore the folding and subsequent function of p53.

This is being tested in clinical trials in combination with other agents. The exact mechanism of action is unknown, states Memarzadeh, which underscores the need for biomarkers of response.