Abstract 2972: Identifying clinically relevant molecular distinctions in gastric cancer development among US minorities to address cancer health disparities

Abstract

Abstract Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. While overall incidence and mortality rates have dropped in recent decades, GC remains a significant health disparity in Hispanic/Latino Americans (HLAs) and in Asian Americans, Native Hawaiians and Pacific Islanders (AANHPIs), who are twice as likely to be diagnosed with and die from GC compared to non-Hispanic whites. In the U.S, these two groups represent the largest and fastest growing minority populations, respectively. Despite such high minority cancer burden, currently there are few FDA-approved targeted therapies for GC, in contrast to dozens of approved targeted therapies for breast, lung, colon, and prostate cancers. The low numbers of GC targeted therapies can be partially explained by limited availability of race/ethnic appropriate cancer genome data and of minority patient-derived models, limiting target identification and drug efficacy studies. Filling these research gaps is crucially important to improve cancer health disparities. Our group has spearheaded the development of the University of California Minority Patient-Derived Xenograft Development and Trial Center (UCaMP) with the goal of addressing these critical issues for GC patient care. In our initial efforts, we have successfully established both patient-derived xenograft (PDX) and organoid (PDO) models for 10 minority GC patient samples. Our PDX and PDO models recapitulate the tumor heterogeneity observed in the patient samples, but also demonstrate varying levels of clonal evolution upon increased time in culture. Importantly, when we performed whole exome, RNA and DNA methylation sequencing on patient tumor and model sample sets, we observe high prevalence of cell cycle regulation/cyclin-dependent kinase (CDK) and PI3K/AKT/mTOR pathway alterations. This is significant, as the FDA has already approved several CDK inhibitors and PI3K/AKT/mTOR inhibitors for other cancer types and even more have shown promise in clinical trials. Indeed, when treat our patient-derived models with these inhibitors, we observe significant responses both in vitro and in vivo. Our findings highlight an important molecular distinction of GC development in racial/ethnic U.S. minorities that provides a rationale for alternative treatments to address GC health disparities that plague these groups and help bring the field closer to precision cancer medicine. Citation Format: Nicole B. Coggins, Hongyong Zhang, Paul Lott, Ana Estrada-Florez, Ted Toal, Alexa Morales Arana, Guadalupe Carvajal, Amanda Kirane, May Cho, Javier Torres, Elizabeth Quino, Sienna Rocha, Rasika Venkatesh, Luis Carvajal-Carmona. Identifying clinically relevant molecular distinctions in gastric cancer development among US minorities to address cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2972.