A new three-year, $2.5 million grant from Stand Up To Cancer® (SU2C) has been awarded to a multi-institutional team of gastroesophageal cancer experts, led by Anil K. Rustgi, MD, director of the Herbert Irving Comprehensive Cancer Center (HICCC) at NewYork-Presbyterian/Columbia University Irving Medical Center. The SU2C-Torrey Coast Foundation Gastroesophageal Cancer Research Team, with collaborators at NYU Langone Health’s Perlmutter Cancer Center and Case Comprehensive Cancer Center (Case CCC), will focus on investigating innovative and effective immunotherapies for esophageal squamous cell cancer (ESCC).
The team at the HICCC, NYU Langone and Case CCC, are part of a greater SU2C Dream Team Collective, which includes three Research Teams of multi-disciplinary experts and across different institutions. The Dream Team Collective aims to rapidly bring new therapies to clinical trials for the treatment of gastroesophageal cancer in diverse populations.
Dr. Rustgi’s collaborators include team co-leader, Kwok-Kin Wong, MD, PhD, director of the Division of Hematology and Medical Oncology at NYU Langone’s Perlmutter Cancer Center and J. Alan Diehl, PhD, chair of the Department of Biochemistry and deputy director at Case CCC. At Columbia, the team also includes Drs. Brian Henick, Hiroshi Nakagawa, Joel Gabre, Jianhua Hu and Hanina Hibshoosh.
“Team science and medicine are critical components of advancing translation of discoveries to eventual patient care,” says Dr. Rustgi, who is also Herbert and Florence Irving Professor of Medicine at Columbia’s Vagelos College of Physicians and Surgeons and chief of the cancer service at NewYork-Presbyterian Hospital. “This ‘dream team’ designation and award underscore the collaborative nature of our team and our aspiration to help our patients, families and communities. The HICCC and our entire team are truly honored.”
Discovering new therapies to treat ESCC
The most common subtype of esophageal cancer is esophageal squamous cell carcinoma (ESCC), which typically has a poor prognosis. Globally, there were an estimated 604,000 new cases of esophageal cancer in 2020, and some 544,000 deaths the same period. Of these cases, 85% were ESCC, the sixth leading cause of cancer-related mortality. While the development of immunotherapy has significantly advanced care for some patients with ESCC, say researchers, most do not durably benefit and need better options.
This team’s work seeks to identify new therapeutic targets to better treat patients with ESCC and broaden the remarkable benefit from immunotherapy for more patients with this cancer type.
With the support from the SU2C award, Dr. Rustgi and collaborators aim to investigate how ESCC cells’ dependence on glutamine metabolism drives their growth and understand how to potentially target that pathway directly in combination with regulators of the cell cycle, namely cyclin D1 and cyclin-dependent kinases (CDK4 and CDK6). This team’s lab work, prior to this effort with SU2C, has led to the launch of an upcoming phase 1 clinical trial at these sites to study an immunotherapy approach to target and eliminate CD38+ myeloid protein and natural killer cells in ESCC (NCT05584709).
Central to the researchers’ goals is to emphasize the development of early career investigators in this area and collaborate closely with patient advocates to tie any advances made seamlessly to real patient care. ESCC disproportionately affects underrepresented minority patients, whose needs the HICCC is well-equipped to serve, notes Dr. Rustgi.
The other lead institutions involved in the SU2C-Torrey Coast Foundation Gastroesophageal Cancer Dream Team Collective include Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, the Broad Institute and Massachusetts General Hospital.
“We hope that our preclinical discovery science,” says Dr. Rustgi, “will lead to clinical trials, which in turn offer hope to fill major gaps in therapy for patients with ESCC and apply to other related cancers, such as head/neck and lung squamous cell cancers.”