The University of Texas Health Science Center at San Antonio (UT Health San Antonio) was recently awarded a $12.6 million program project grant (P01) from the National Institutes of Health’s National Cancer Institute to expand collaborative efforts to explore the biological mechanisms of BRCA1, BRCA2 and related tumor suppressors and to shed light on potential new cancer treatments.
“This investment in research is a commitment to pioneering treatments in cancer care,” said Lei Zheng, MD, PhD, executive director of Mays Cancer Center at UT Health San Antonio. “The funding supports our mission to make significant strides in bringing hope and fighting cancer.”
Research into BRCA1, BRCA2 and related gene mutations connected to familial breast and ovarian cancers has led to highly effective treatments that work in most patients. Still, many patients must contend with tumor reoccurrence, and in some cases these tumors become broadly resistant to a variety of treatments, said Patrick Sung, DPhil, program leader for this five-year grant.
Sung, director of the health science center’s Greehey Children’s Cancer Research Institute, associate dean for research with the Joe R. and Teresa Lozano Long School of Medicine, professor of biochemistry and structural biology and the Robert A. Welch Distinguished Chair in Chemistry, is a world-leading expert in the roles of BRCA1 and BRCA2 in DNA repair.
According to Sung, mutations in BRCA1 and BRCA2 can lead to breast, ovarian, prostate and other cancers. Mutations in these genes affect one in every 200-300 people, amounting to more than one million carriers of these mutations in the United States alone.
Current treatments, such as FDA-approved polyADP ribose polymerase inhibitors (PARPi) and platinum-based chemotherapy are, in general, effective for most patients. However, many of the treated patients eventually develop resistance to these drugs when disease recurs, said Sung. Understanding the processes that cause drug resistance is crucial for determining which treatment option would be most appropriate and for driving the development of new therapeutic approaches.
“By working together as a team, we greatly enhance the impact of what we do,” Sung said.
Sung said this grant, the largest of his career, allows UT Health San Antonio and the Greehey Children’s Cancer Research Institute to assemble some of the best scientists in the world to create a comprehensive framework for elucidating the biological mechanisms of DNA damage repair and how BRCA gene mutations affect repair efficiency.
“This program project grant is a testimony that we are working well together and doing impactful work as a multidisciplinary team. This investment will continue to enhance synergy among project investigators,” Sung said.
Trying to find treatments for cancer without knowing the biology behind it is like searching for a key in a darkened room, said Sung. Understanding the scientific underpinnings is like turning on the light.
Program project grants include a supported network of research projects and core facilities collaborating to share knowledge and resources. Each project makes unique contributions to the overall goal.
Research projects and core facilities
The program includes an administrative core, three shared resource cores and three projects. All components will be led by UT Health San Antonio scientists except for project 1, led by Dipanjan Chowdhury, PhD, and Panagiotis (Panos) Konstantinopoulos, MD, PhD, from the Dana-Farber Cancer Institute in Boston.
The leader of project 2 is Sandeep Burma, PhD, professor of neurosurgery. Sung and Eric Greene, PhD, professor of biochemistry and molecular biophysics at Columbia University, New York City, are co-investigators.
Project 3 co-leaders are Alexander Mazin, PhD, professor of biochemistry, and Weixing Zhao, PhD, assistant professor of biochemistry. Greene is a co-investigator.
The first core will be protein biochemistry and enzymology, headed by Youngho Kwon, PhD, associate professor of biochemistry.
The second core is chromosome replication and analysis, led by Robert Hromas, MD, acting president of UT Health San Antonio.
The third core is structural biology and biophysics, headed by David Libich, PhD, associate professor of biochemistry.
“By strengthening the basic sciences, we will establish a linkage between research and clinical translation in a seamless manner,” Sung said.