The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation has funded an ambitious initiative to overcome one of the most perplexing and frustrating mysteries of cancer treatment — how to prevent drug resistance.
Patients treated for cancers can have robust responses to drugs, particularly targeted therapies and chemotherapies, before molecular changes within the cancer cells render the drugs ineffective. The foundation has awarded a three-year grant to support research led by Houra Merrikh, PhD, professor of Biochemistry, and Ben Ho Park, MD, PhD, the Benjamin F. Byrd Jr. Professor of Oncology and director of Vanderbilt-Ingram Cancer Center, to create an anti-evolution drug to reduce the capacity of cancer cells to develop resistance.
Merrikh and Juan Carvajal-Garcia, PhD, a postdoctoral fellow in her lab, have identified the molecular pathway by which bacteria develop antibiotic resistance — research that was published in July in The Proceedings of the National Academy of Sciences. The grant allows them to now focus on cancer therapy resistance.
“There is an analogous pathway in cancer,” Merrikh said. “We have pinpointed a specific protein in that pathway that we think, if we can inactivate it, is very likely to lessen the mutation load and potentially reduce the occurrence of drug resistance in the treatment of cancer. If we are right, it would be a really novel angle on how to treat cancer and alleviate a big problem in the clinic.”
The foundation, which is based in Texas, funds medical research that is innovative and groundbreaking with distinctive and novel approaches.
The foundation’s investment in this high-risk, high-reward initiative provides immediate seed funding for basic sciences research in the A.B. Hancock Jr. Memorial Laboratory for Cancer Research, which focuses on advancing early-stage discovery and innovation. The Hancock Lab recently celebrated its 50th anniversary, and a $2 million fundraising initiative is ongoing to continue that mission through The Waddell Walker Hancock Cancer Discovery Fund.
“Funding from foundations and other private-sector donors is integral to Vanderbilt’s mission to create the knowledge and medical discoveries that lead to new and better treatments for cancer and other diseases,” said Jennifer Pietenpol, PhD, Executive Vice President for Research, Chief Scientific and Strategy Officer for Vanderbilt University Medical Center and holder of the Brock Family Directorship in Career Development. “This type of support nurtures paradigm-shifting research that can translate to innovation in patient care.”
The foundation has supported cancer research at Vanderbilt for the last 50 years, starting with a gift in 1972 to the A.B. Hancock Jr. Memorial Laboratory for Cancer Research when it was newly established. To date, the foundation has provided nearly $25 million in support.
“We are very proud of our investments at Vanderbilt-Ingram Cancer Center starting with our initial gift 50 years ago in memory of Arthur “Bull” Hancock,” said Helen Alexander, President of the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation. “In keeping with the vision of Bob and Helen Kleberg, we have awarded competitive grants to researchers at Vanderbilt-Ingram that have questioned the prevailing paradigm and led to advancement of knowledge in the field,” she said.
“We are grateful to the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation for their legacy of support, and we are also very proud and appreciative of the researchers whose work has garnered that support. Grants from the foundation are highly competitive,” said Larry Marnett, PhD, Dean Emeritus for Basic Sciences at Vanderbilt University School of Medicine, and the Mary Geddes Stahlman Professor of Cancer Research.
The foundation’s most recent previous grant came in 2021 to support the project “Revisiting a formidable foe: Defining a new pathway to treat MYC-driven cancers.” Other awards provided crucial funding for Vanderbilt-Ingram’s renowned Breast Cancer Program. A center in genomics named for the foundation was launched in 2000 and renamed the Robert J. Kleberg, Jr. and Helen C. Kleberg Center for Personalized Cancer Medicine in 2008.
A gift for upper aerodigestive research in 2006 supported a significant expansion of the Thoracic, GI and Head and Neck Cancer Programs, and in 2008, the foundation’s support for Vanderbilt-Ingram’s imaging program helped foster the development of novel radiochemical probes for positron emission tomography (PET) scanning and the use of advanced research imaging to track the delivery and effectiveness of cancer therapies.
“The work that Dr. Merrikh is leading in her lab is bold and an outside-the-box approach to improving cancer therapies. The goal of preventing drug resistance to cancer therapies provides hope for both cancer clinicians and their patients,” Park said.
Merrikh said she’s greatly appreciative to receive the financial support.
“We have faced challenges obtaining funding from traditional routes because our research idea is very different and, also, we have not previously worked on cancer,” she said. “The inquiry is somewhat too innovative for traditional funding sources. It gives me encouragement that there is a foundation willing to fund high-risk, high-rewards projects. We are grateful that the foundation believes in our ability to research and potentially implement this game-changing idea.”
by Tom Wilemon
VUMC Reporter, Sep.1, 2023