Sanaz Memarzadeh, MD, PhD, professor with tenure, gynecologic cancer surgeon, Department of Obstetrics and Gynecology, University of California Los Angeles (UCLA) Ronald Reagan Hospital, gynecologic oncology staff and gynecologic cancer surgeon, VA Hospital, director, G.O. Discovery Laboratory, UCLA Broad Stem Cell Research Center, affiliate oncologist, The Ovarian Cancer Circle Inspired by Robin Babbini, UCLA Health, discusses the potential for frontline combination therapy regimens in ovarian cancer. 

Although platinum-based therapies are effective in treating patients with ovarian cancer, patients often relapse, Memarzadeh explains. One reason for these relapses could be that a pre-existing population of tumor cells that are resistant to therapy repopulate the cancer after being dormant. As such, utilizing combination therapies in the frontline setting could target this cell population and prevent relapses, Memarzadeh says.

Clinical trials are needed to evaluate such combinations in patients with ovarian cancer, who often present with advanced-stage disease and are eligible for neoadjuvant chemotherapy. As such, patients could be treated with standard chemotherapy combined with biologic agents to potentially target the resistant tumor cell population, Memarzadeh says.

Notably, these clinical trials should be well-designed and incorporate extensive translational end points to provide insight into the tumor cell populations. Although funding remains an unmet need for these studies, frontline combination strategies could effectively cure patients early and prevent disease recurrences, Memarzadeh concludes.

Videos

Sanaz Memarzadeh, MD, PhD, discusses the potential for frontline combination therapy regimens in ovarian cancer.  



Dr. Memarzadeh on the Potential for Frontline Combinations 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 

 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.

Dr. Memarzadeh on p53 Reactivation in Ovarian Cancer

Sanaz Memarzadeh, MD, PhD, associate professor of Obstetrics and Gynecology, and the director of the Gynecologic Oncology Discovery Lab at UCLA, discusses her preclinical research on resistant tumor cells in ovarian cancer.

The majority of patients with ovarian cancer present with advanced stage disease, and despite undergoing radical surgeries and chemotherapy, many patients relapse, says Memarzadeh. It was not previously understood why this was the case, says Memarzadeh.

However, by analyzing primary tumors from patients who presented with ovarian cancer, Memarzadeh and her team at UCLA found that, while most tumor cells respond to chemotherapy, there is a subset that resist standard treatments. These resistant cancer cells are there from the beginning in most primary ovarian cancer tumors, says Memarzadeh, and they do not express the most common biomarker used for the detection of ovarian cancer. They also have the ability to quickly reinitiate the cancer, she adds.

Sanaz Memarzadeh, MD, PhD, associate professor of Obstetrics and Gynecology, and the director of the Gynecologic Oncology Discovery Lab at UCLA, discusses her preclinical research on resistant tumor cells in ovarian cancer. 

Dr. Sanaz Memarzadeh on Chemotherapy Resistant Tumor Cells in Ovarian Cancer

Sanaz Memarzadeh, MD, PhD, gynecologic oncology, obstetrics and gynecology, University of California, Los Angeles, discusses recurrence rates in ovarian cancer.

The challenge with epithelial ovarian cancer, Memarzadeh says, is that the majority of patients present with advanced disease due to lack of identified biomarkers and little to no symptoms.

Therefore, in patients with stage III to IV epithelial ovarian cancer, approximately 80% to 85% relapse, despite undergoing surgeries and/or chemotherapy.

Sanaz Memarzadeh, MD, PhD, gynecologic oncology, obstetrics and gynecology, University of California, Los Angeles, discusses recurrence rates in ovarian cancer.


Dr. Memarzadeh on Recurrence Rates in Ovarian Cancer

Sanaz Memarzadeh, MD, PhD associate professor of obstetrics and gynecology and the director of the Gynecologic Oncology (GO) discovery Lab at UCLA, discusses the benefits of hormonal therapy for endometrial tumors.

Endometrial tumors are hormonally regulated, but hormonal therapy is not widely used to treat this subtype. This is mainly due to a lack of understanding of its effects, said Memarzadeh. 

	Memarzadeh’s team determined that supporting stromal cells surrounding an endometrial tumor which  are most commonly ignored, are the cells that exert the progesterone  anti-cancer effects.

Sanaz Memarzadeh, MD, associate professor of obstetrics and gynecology and the director of the Gynecologic Oncology (GO) discovery Lab at UCLA, discusses the benefits of hormonal therapy for endometrial tumors.

Sanaz Memarzadeh, MD, PhD

Articles

Dr. Memarzadeh on the Potential for Frontline Combinations in Ovarian Cancer

Dr. Memarzadeh on p53 Reactivation in Ovarian Cancer

Dr. Sanaz Memarzadeh on Chemotherapy Resistant Tumor Cells in Ovarian Cancer

Dr. Memarzadeh on Recurrence Rates in Ovarian Cancer

Dr. Memarzadeh on Hormonal Therapy for Endometrial Tumors