Early detection of pancreatic cancer is notoriously difficult, making it one of the deadliest forms of the disease, with a 5-year survival rate of approximately 10 percent. By the time symptoms appear, surgery is not a viable option for the majority of patients, and chemotherapy offers limited improvement in survival. Identifying new treatments is crucial for improving outcomes for patients.
In an effort to bring new compounds to the pancreatic cancer drug development pipeline, Alec Kimmelman, MD, PhD, a professor in and the Anita Steckler and Joseph Steckler Chair of the Department of Radiation Oncology at NYU Grossman School of Medicine and a member of the senior leadership team at NYU Langone Health’s Perlmutter Cancer Center, has received a $1.7 million Drug Discovery Award from The Mark Foundation for Cancer Research. Dr. Kimmelman shares the award with Seth Parker, PhD, an assistant professor of biochemistry and molecular biology at the University of British Columbia and a former postdoctoral researcher in his NYU Langone lab. The team aims to identify a first-in-class small molecule inhibitor of the amino acid transporter SLC38A2/SNAT2, a novel target for pancreatic cancer.
The Mark Foundation’s Drug Discovery Award program is designed to accelerate the conversion of promising scientific discoveries into therapeutics that will benefit people with cancer. Launched in 2020, the program supports high-risk, high-reward research and aims to bridge the “Valley of Death” that dooms so many early drug discovery efforts.
“The treatment options for patients with pancreatic cancer remain very limited, and any novel targets warrant significant study,” Dr. Kimmelman said. “The support from The Mark Foundation will allow us to build on our initial discoveries for our shared goal of impacting patient care.”
The team’s project focuses on identifying candidate inhibitors of the transporter by screening a large chemical library using a sophisticated high-throughput, mass spectrometry–based tool developed by Evotec, a drug discovery and development company headquartered in Germany.
Dr. Kimmelman is a world leader in the cancer metabolism field and has made critical discoveries that have identified novel metabolic pathways in pancreatic cancer. His research focuses on the unique metabolism of pancreatic cancers to understand how they use various fuel sources to power their growth.
In a study published in 2016 in Nature, Dr. Kimmelman’s lab showed that one of the ways that pancreatic cancers obtain nutrients is by sharing them with cancer-associated fibroblasts, the connective tissue–forming cells in the tumor microenvironment that promote tumor development. Under nutrient stress, the researchers found that cancer-associated fibroblasts secrete the amino acid alanine, which pancreatic cancer cells use as a source of fuel to proliferate and produce the building blocks that they need for survival.
In a study published in 2020 in Cancer Discovery, Dr. Parker led a team of researchers in Dr. Kimmelman’s lab that showed SLC38A2/SNAT2 is expressed by pancreatic cancer cells and is responsible for allowing transport of alanine into the tumors. Dr. Parker and his colleagues found that genetically targeting this transporter creates a metabolic crisis in cell cultures of pancreatic tumor cells, rendering them unable to grow. The researchers also showed that targeting SLC38A2/SNAT2 in animal models using genetic tools such as CRISPR shrinks pancreatic tumors.
In addition to The Mark Foundation grant, the project is supported by funds from Technology Opportunities and Ventures, the technology commercialization arm of NYU.
“The support from The Mark Foundation, combined with the investment from NYU, enables us to embark on a campaign to develop a pharmacological inhibitor of SLC38A2/SNAT2 and test it in preclinical models,” Dr. Kimmelman said. “Our ultimate goal is to bring a compound forward for the clinical development of a treatment for pancreatic cancer.”