UC Davis Comprehensive Cancer Center has received a $6.3 million grant from the National Cancer Institute’s (NCI) Center to Reduce Cancer Health Disparities for a 5-year study to tease out why some ethnic and racial minority groups fare worse than whites when they get cancer and to find more precise treatments to improve their chances of survival.
The new, collaborative study engages four of the University of California’s NCI-designated comprehensive cancer centers: UC Davis Comprehensive Cancer Center, Jonsson Comprehensive Cancer Center at UCLA, UCSF Helen Diller Family Comprehensive Cancer Center and the Chao Family Comprehensive Cancer Center at UC Irvine. The four centers are part of the recently created UC Cancer Center Consortium, and their patient population is among the most diverse in the U.S.
Under the grant, entitled “University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center” or UCaMP, tumor samples from patients will be delivered to UC Davis for use in the research. A minimum of 60 percent of the tumor samples will be drawn from minority patients to grow tumors (or xenografts) in mice; the rest will be from non-Hispanic whites and used as controls. Once a PDX is established, it can be replicated so that a single patient tumor can be used to test numerous drugs at the same time. The goal is to generate at least 200 PDXs for use in two research projects. The findings will be shared with the NCI and other scientists to aid in the development of more precise cancer treatments.
The study will focus on four types of cancer that disproportionately affect minorities: lung, liver, gastric (stomach) and bladder. The first project in the study will focus on gastric and liver cancer among Latinos and Asian Americans, Pacific Islanders and Native Hawaiians, and the second will examine lung and bladder cancers among African Americans. Researchers will use PDXs to discern their genetic characteristics and to test potential targeted drugs to treat them.
“UCaMP is one of the only two programs funded by NCI nationwide to address cancer health disparities using patient-derived cancer models,” said Chong-xian Pan, a study principal investigator. Pan is a medical oncologist and physician-scientist specializing in genitourinary cancers. He will coordinate the study’s annual report to the NCI and oversee the bladder and lung cancer project.
When compared with non-Hispanic whites, African Americans have lower survival from lung and bladder cancer, even when diagnosed at the same stage of the disease.
“We are trying to address why this happens,” Pan said. “Socio-economics could be a factor, but we also want to see if there are biological factors contributing to this disparity. PDXs are a great model, not only to study the biological differences of cancers from non-Hispanic whites and African Americans, but also to facilitate cancer drug development and precision medicine.”
Luis Carvajal-Carmona, a UC Davis cancer genomicist, expert in the genetics of Latinos and a principal investigator, will lead the stomach and liver cancer project. He said the study is an effort to correct a major discrepancy in existing cancer genomics research to date – the lack of minority patient representation, which is essential for the development of targeted, or personalized, treatments.
“Minority patients have the worst cancer outcomes for multiple reasons,” he said. “One of them is because they come in with more advanced tumors because many don’t have proper access to health care. But also because there are not enough data and models for the scientific community to develop precision medicine studies in them. So we want for this NCI-funded research to be a magnet for minority-focused clinical trials.”
Carvajal-Carmona said that while gastric cancer is a leading cancer killer of Latinos, the largest gastric cancer genetic sequencing study to date, which analyzed 300 tumors, included only three tumor samples from patients of Latino ancestry.
“Sequencing studies are done to find targets (genetic mutations) to help develop new therapies, and because Latinos have different genetic backgrounds and may have different lifestyles and environmental risk factors, their tumors are likely to be different, too, which will affect the targets for treatment.”
Moon Chen, a UC Davis population scientist, expert in Asian cancer health disparities and a principal investigator, said PDXs have advantages over other research tools because they can be used to screen for and enhance the effectiveness of cancer therapies or to develop novel therapies.
“In so doing, they contribute to a better understanding of the underlying mechanisms of resistance and elucidate potential biological determinants of treatment responses and cancer health disparities for these tumor sites,” he said.
UC Davis researchers have used PDX models to study potential cancer therapies for many years, mostly in collaboration with The Jackson Laboratories, an NCI-designated cancer research center. Although all of the mouse work for the current study will be done at UC Davis and UCSF, The Jackson Laboratories also was awarded an NCI grant to serve as the coordinating center for this and other PDX research.
Other investigators involved in the study are Ralph de Vere White, David J. Segal, Regina Gandour-Edwards, K.C. Kent Lloyd, John Albeck, David R. Gandara, Kit S. Lam, Ai-Hong Ma, Edward N. Pugh, David M. Rocke, Susan Leroy Stewart and Clifford G. Tepper of UC Davis; Roshan Bastani, Samuel French and Richard S. Finn at UCLA; Robert E. Bristow, Farshid Dayyani and Marian Waterman at UC Irvine; and Rosemary J. Akhurst, Robert A. Hiatt, John Gordan, R. Kate Kelley and Tung Nguyen at UCSF.
The project will be funded with NCI grant No. 1 U54 CA233306-01.
UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its specialists provide compassionate, comprehensive care for more than 10,000 adults and children every year, and access to more than 400 clinical trials at any given time. Its innovative research program engages more than 300 scientists at UC Davis, Lawrence Livermore National Laboratory and Jackson Laboratory (JAX West), whose scientific partnerships advance discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis collaborates with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer care. Its community-based outreach and education programs address disparities in cancer outcomes across diverse populations. For more information, visit cancer.ucdavis.edu.