Women's Research Day 1: Discoveries in Cancer

Early-phase clinical trials produce effective treatments in a significant number of cases. And ovarian cancer sometimes begins in the fallopian tubes, not in the ovaries.

Those were just two of the fascinating facts presented by Cedars-Sinai investigators Monica Mita, MD, and IIana Cass, MD, at the first of two Women's Research Day events in March. The presentations, organized by Academic Affairs in honor of National Women's History Month, highlighted the work of prominent female scientists at Cedars-Sinai. About 150 people attended each event in Harvey Morse Auditorium.

"Our inaugural event last year was so popular that we decided to offer the community two opportunities this year to hear about the exciting research that is being conducted by a few of our women faculty members," said Nicole Leonard, vice president and associate dean, Research Administration.

Mita, professor of Medicine and co-director of the Experimental Therapeutics Program at Cedars-Sinai Cancer, discussed the increasing prominence of Phase 1 clinical trials of cancer drugs. Cass, professor and vice chair of the Department of Obstetrics and Gynecology, discussed her research on genetic mutations associated with ovarian cancer.

In her presentation, Mita explained that Phase 1 clinical trials, designed to evaluate the safety and correct dosage for potential treatments, are getting better at also showing efficacy. In some populations, 25 percent or more of the subjects respond to the treatment being tested in Phase 1 trials.

"We have the privilege to see the first responders with a new drug," said Mita, whose program is currently overseeing more than 10 Phase 1 cancer trials. "We sometimes see incredible results."

Her current work includes:

A follow-up study on a drug that counters abnormalities in TRK protein receptors that are associated with certain cancers.
A study that deploys two drugs against breast cancer: niraparib, a so-called PARP inhibitor, which promotes the death of cancer cells by keeping them from repairing their damaged DNA; and pembrolizumab, a type of immunotherapy, which helps the body's own immune system recognize and attack the cancer.
A trial focusing on a compound that inactivates an enzyme to help improve how the body metabolizes fat. "Overweight and obesity are implicated in 15 to 20 percent of cancer-related deaths," Mita explained.

For the future, Mita sees more Phase 1 trials that combine different potential therapies into a single study. The need is urgent, given that more than 1,500 people in the U.S. die each day from cancer, she said. "If we don't change the way we are treating cancer, 25 percent of our current population will die of cancer," Mita said.

Cass discussed her research involving mutations in the BRCA1 and BRCA2 genes, which are associated with increased risk for ovarian cancer and breast cancer. Cass focuses on ovarian cancer, a relatively rare but deadly type, in which inheritable genetic mutations account for about a fifth of the cases.

Cedars-Sinai provides a major opportunity to study BRCA1 and BRCA2 mutations because they are more common in Jewish women than in non-Jewish women, and about 30 percent of Cedars-Sinai's female patients are Jewish, Cass explained. Ovarian cancer in patients with these mutations has specific characteristics.

Research has shown that some ovarian cancers originate in the fallopian tubes or the peritoneum—a single cell layer that lines the pelvic and abdominal cavity. In her own work, Cass said, she has shown that women with BRCA1 mutations are more likely than other women to have hidden cancer developing in the fallopian tubes. "Removing the fallopian tubes in BRCA1 mutation carriers could prevent a lot of cancer after age 40," she said.

One concern about such surgery, which is sometimes performed along with ovary removal as a risk-reducing measure by women with this mutation, is that it can have negative side effects, especially in younger women. Cass and colleagues are currently studying the short-term impact of so-called surgically induced menopause on cognitive function, cardiovascular disease and other aspects of well-being.

Cass concluded her talk by tracing changes over the years in the state of knowledge about cancer.

"Twenty years ago we understood how to take care of cancer just by looking at the patient and the histology of her cancer," she said. "Now, by understanding the genetic mutations that underlie these cancers, we can move towards targeted therapies, maximize outcomes, minimize side effects and ultimately try to understand better prevention in this patient's family."