April 30, 2015

VICC cancer research efforts in spotlight at AACR conference

Adding an investigational drug to an already approved estrogen blocking therapy appears to be safe and provided clinical benefit for some postmenopausal women with estrogen-positive breast cancer.

Adding an investigational drug to an already approved estrogen blocking therapy appears to be safe and provided clinical benefit for some postmenopausal women with estrogen-positive breast cancer.

The research led by Ingrid Mayer, M.D., associate professor of Medicine and clinical director of the Breast Cancer Program at Vanderbilt-Ingram Cancer Center (VICC), was selected for the press program during the American Association for Cancer Research (AACR) Annual Meeting, held recently in Philadelphia.

A record number of VICC investigators presented their cancer-related research findings during the international conference, which attracted thousands of researchers, health care professionals and patient advocates.

Carlos Arteaga, M.D., director of the Center for Cancer Targeted Therapies and director of the Breast Cancer Program at VICC, has served as AACR president for the past year and during the conference he transferred the reins to the incoming president, José Baselga, MD., Ph.D., from Memorial Sloan Kettering Cancer Center.

“I have been deeply honored to serve in this top leadership post for the largest cancer research organization in the world,” Arteaga said. “Working closely with the world’s premier cancer investigators as we seek to enhance our knowledge of this disease has been very rewarding and has also highlighted the caliber of the research being done here at VICC.”

That research includes Mayer’s Phase 1b study, which focused on combination therapy for women whose breast cancer is fueled by estrogen. Antiestrogen therapies are the standard of care for patients with ER-positive breast cancer, but in many cases the patient’s cancer becomes resistant to this therapy.

“Preclinical studies have shown that ER-positive breast cancer cells frequently use the PI3K signaling pathway to circumvent the effects of antiestrogen therapy and that adding a PI3K inhibitor to an antiestrogen can restore the sensitivity of ER-positive breast cancer cells to these drugs,” said Mayer.

The study combined the PI3K inhibitor drug known as BYL719 (alpelisib) with aromatase inhibitor drug letrozole. Latest analysis of the data showed 19 percent of patients had a partial response and 43 percent had stable disease. Thirty-five percent had a clinical benefit lasting for more than six months and 30 percent had clinical benefit for over 12 months. This work was also highlighted in Arteaga’s Presidential address, which focused on mechanisms of resistance to endocrine therapy in ER-positive breast cancer.

Based on these early results, investigators plan to test the drug combination in a Phase III clinical trial that will soon start accrual of patients.

Determining potential targets for triple negative breast cancer (TNBC) was the focus of an AACR presentation by Jennifer Pietenpol, Ph.D., director of VICC. Triple negative breast cancer is not driven by the hormones estrogen or progesterone or the HER2-neu protein and is one of the most aggressive forms of breast cancer. Pietenpol and her colleagues have already identified multiple subtypes of  TNBC and are working to identify potential treatments for those subtypes.

Valerie Jansen, M.D., Ph.D., clinical oncology fellow in the laboratory of Arteaga and recipient of a VICC Brock Fellowship, presented an abstract selected for oral presentation on mechanisms of resistance to CDK4/6 inhibitor drugs in breast cancer.

Daniel Liebler, Ph.D., professor of Biochemistry, Pharmacology and Biomedical Informatics, and Robbert J.C. Slebos, Ph.D., research associate professor of Biochemistry and Cancer Biology, each discussed the role of proteomics in cancer research.

Lawrence Marnett, Ph.D., Mary Geddes Stahlman Professor in Cancer Research and associate vice chancellor for Research, discussed the potential role of aspirin and other non-steroidal anti-inflammatory drugs in cancer.

And Yu Shyr, Ph.D., director of the Center for Quantitative Sciences, led sessions on the role of big data in cancer research.