Upper gastrointestinal (GI) malignancies are among the most lethal tumor types, contributing to over one million deaths worldwide in 2023 from the combined toll of gastric and esophageal cancers. These tumors present formidable challenges in diagnosis, treatment, and outcomes, underscoring the urgent need for innovative approaches to enhance patient care and survival.

The AACR-Torrey Coast Foundation Transpacific Gastric and Esophageal Cancer Research Partnership Grant is intended to support a multi-institutional team with principal investigators from at least one institution in the United States and one in Asia. The focus is on collaborative research in gastric or esophageal cancer, specifically in areas such as resistance, metastasis, innovative treatment strategies (including identifying and characterizing novel targets), and cellular and immunotherapies.

2026 Grantees

Scientific Statement of Research

The survival for advanced gastroesophageal cancers remains poor and current immune checkpoint inhibitors provide modest survival gains for some patients. T-cell engagers represent a promising alternative strategy by physically linking T cells to tumor antigens independent of peptide–MHC presentation or T-cell receptor α/β chains, potentially overcoming key mechanisms of resistance. Using a patient-derived organotypic spheroid system, Drs. Klempner and Lee previously demonstrated enhanced EpCAM×CD3 T-cell engager–mediated cytotoxicity when combined with co-targeting immunomodulatory circulating factors. To define mechanisms of resistance and identify biomarkers to guide patient selection, Drs. Klempner and Lee will evaluate combination strategies in a zero passage ex vivo culture system. They will also assess effects on T-cell activation and cytotoxic function. In parallel, they will characterize the tumor–immune microenvironment and target antigen evolution during T-cell engager therapy using single-cell RNA sequencing and multiplex immunofluorescence on serial patient samples.

Biographies

Dr. Klempner earned his medical degree from the University of Massachusetts Medical School and completed his residency at the Brigham and Women’s Hospital, followed by a medical oncology fellowship at Beth Israel Deaconess Medical Center. During his training, he conducted research at Harvard. He is currently an Associate Professor at Massachusetts General Hospital and Harvard Medical School where he holds the Tobins Family Endowed Chair in Esophagogastric Cancer and leads the gastroesophageal cancer research program. His research focuses on understanding intrinsic and acquired resistance to targeted and immune therapies, as well as dissecting the tumor microenvironment to identify novel therapeutic approaches and biomarkers in gastroesophageal cancers.

Dr. Lee earned her medical degree at Ewha University in Seoul, South Korea. She is a medical oncologist, taking care of gastric cancer patients, a Director of Samsung Precision Genomics Medicine Institute at Samsung Medical Center and a professor in medical oncology. Her research focuses on biomarker-driven clinical trials and implementation of personalized medicine in advanced solid tumors. She has implemented a genome-based matched trial focusing on gastric/GEJ cancer and has led several global research projects over the past decade in precision oncology.

Acknowledgement of Support

“Gastric and esophageal cancers are a global problem that need a global solution. The AACR-Torrey Coast Foundation Transpacific Gastric and Esophageal Cancer Research Partnership Grant is a transformative step toward increasing Dr. Lee and my collaborations to accelerate bringing new therapies and understanding to a difficult cancer that needs more options.”

Scientific Statement of Research

Diffuse gastric cancer (DGC) is an aggressive malignancy characterized by rapid infiltrative growth, stromal fibrosis, immune suppression, and limited responsiveness to immune checkpoint blockade. Despite advances, effective treatment options for DGC remain scarce. Emerging evidence indicates that neural components of tumor microenvironment regulate tumor progression and immune evasion, yet, the interplay between neurogenic signaling and myeloid-driven immune suppression in DGC has not been systematically investigated. In this collaborative project, Drs. Wang and Hayakawa will use mouse models and orthotopic transplantation systems that recapitulate patho-immunological features of human disease to characterize neural innervation, immune composition, and epithelial–stromal niche architecture during disease progression. They will focus on how activation of the calcitonin gene-related peptide signaling axis, a sensory nerve pathway implicated in immune suppression, shapes the immunosuppressive tumor microenvironment. Together, these studies will define the broader neuro–immune regulatory network in DGC and provide a preclinical foundation for developing improved therapeutic strategies.

Biographies

Dr. Wang earned his undergraduate degree in Chemistry from Williams College and his medical degree from Columbia University. He completed his residency at Washington University and fellowship at Harvard Medical School. He is the Silberberg Professor and Vice-Chair of Academic Programs in Medicine at Columbia, where his laboratory investigates molecular mechanisms of gastrointestinal disorders.

Dr. Hayakawa earned his medical degree and doctoral degree from the University of Tokyo, where he completed training in internal medicine and gastroenterology. He pursued postdoctoral research at Columbia University under Timothy C. Wang, studying gastrointestinal stem cells and cancer biology. He returned to the University of Tokyo, where he is currently ian Associate Professor in the department of gastroenterology. His research focuses on gastrointestinal cancer initiation and progression, particularly stem cells, tumor microenvironments, neuroimmune interactions, and translational oncology.

Statement of Support

“The AACR-Torrey Coast Foundation Transpacific Gastric and Esophageal Cancer Research Partnership Grant provides a unique opportunity to bring together the complementary expertise of the Wang laboratory at Columbia University and the Hayakawa laboratory at the University of Tokyo to understand the neuro-immune regulatory network in diffuse gastric cancer and uncover innovative therapies to treat the disease.”