With the help of two major grants, Dr. Marina Holz, the Doris and Ira Kukin Professor of Biology at Yeshiva University’s Stern College for Women, is exploring new treatment options for patients with rare and little-understood forms of cancer.

This fall, Holz will partner with colleagues at the University of Cincinnati in a new clinical trial that examines the potential role of a drug combination therapy to eliminate lymphangioleiomyomatosis (LAM) cells, funded by a three-year, $712,442 grant from the National Institute of Health’s (NIH) Heart, Lung and Blood Institute. LAM is a rare but serious lung disease that occurs primarily in women of childbearing age as a low-grade tumor in which the abnormal tumor cells grow out of control and spread to restricted areas in the body, including the lungs, kidneys, lymph nodes, blood vessels and lymphatics.

The trial will look at the safety and efficacy of a combined therapy using sirolimus and resveratrol as a potential remission-inducing treatment option for patients with LAM. Sirolimus is a drug approved by the Food and Drug Administration that suppresses cell growth in LAM patients and is currently the first-line treatment option for most LAM patients. Resveratrol is a naturally occurring chemical found in the skin of grapes used to make red wine.

Pre-clinical research conducted by Holz demonstrated that the combination of the two can kill LAM cells.

“I am thrilled that this grant will allow us to rapidly build upon the basic and preclinical studies that started in my lab in 2014 and led to a synergistic collaboration with our clinical partners at University of Cincinnati, and our industry partner Evolva, the provider of resveratrol,” says Holz. “This grant will allow us to make substantial progress towards validating new therapeutic options for treatment of LAM, and will serve as a model of cross-disciplinary collaboration and rapid implementation of future clinical trials.”

In addition, Holz has received a three-year, $501,000 NIH grant to examine the role played by estrogen-related receptor alpha in triple-negative breast cancer (TNBC), an aggressive, metastatic form of the disease more likely to affect younger people, African Americans, Hispanics and those with a BRCA1 gene mutation. Patients with TNBC lack the receptors that have been most successfully targeted by current breast cancer treatments, leaving standard chemotherapy as their only treatment option.

But estrogen-related receptor alpha is overexpressed in TNBC patients, and Holz believes that a better understanding of its role may suggest the use of different drugs that can effectively target the receptor to improve prognosis. “The wealth of the generated knowledge will allow us to establish a long-term research project to identify putative cellular targets to be studied in greater detail with the goal of exploring new avenues in breast cancer research, and develop new interventions and prognostic markers of therapy response,” said Holz. “Expanding the use of tamoxifen and rapamycin, both safe and FDA-approved drugs, may clinically benefit millions of women suffering from TNBC, with the potential to reduce disease mortality.”