Exploiting Cancer's Metabolic Vulnerabilities

The Lustgarten Foundation advances intrepid and innovative work


Early in his career, Whitehead Member David Sabatini discovered the mTOR protein. mTOR stands for mechanistic target of Rapamycin (an immunosuppressant drug that inhibits cell growth) and the pathway has proven extremely important in cell metabolism. Sabatini’s ongoing efforts to define the mTOR pathway’s effects on cell growth are leading to potential treatments for a range of medical conditions—from tuberous sclerosis complex, which causes autism-like symptoms and benign tumors, to many forms of cancer.
Indeed, because malignancies often grow and proliferate quickly, identifying metabolic vulnerabilities could prove to be an especially productive path to new cancer therapies. Recently, Sabatini’s lab uncovered a potential vulnerability in pancreatic cancer. They have found that the loss of the cellular protein SLC38A9, which helps transport amino acids, severely impairs the proliferation of pancreatic cancer cells in culture and in mice. “The loss of SLC38A9 appears to reduce the availability of specific amino acids that those cells use for fuel,” Sabatini explains. “We’re now investigating exactly why the loss of SLC38A9 has that effect in cancer cells. In parallel, we are screening for compounds with similar effects—which may yield a drug that starves pancreatic tumor cells while leaving normal cells unaffected.”
This pathbreaking study was underwritten by a three-year, $1 million grant from the Lustgarten Foundation, which was impressed by Sabatini’s record of discovery and by the promise inherent in his SLC38A9 hypothesis. The largest private funder of pancreatic cancer research, the Foundation supports world-class scientists striving to understand the disease’s development and to uncover new treatments.
“We are relentlessly focused on improving patient outcomes by supporting world-class basic and clinical research,” explains the Foundation’s President and CEO, Kerri Kaplan. The Foundation was created and named in honor of Marc Lustgarten, the late Vice Chairman of Cablevision, Inc. who died of pancreatic cancer in 1999. At that time, pancreatic cancer was an “orphan” disease: The National Cancer Institute’s (NCI) spent less than $16.2 million on the disease, supporting fewer than 15 investigators. “Since 1998, the Lustgarten Foundation has made more than $165 million in research awards,” Kaplan notes.
“Those investments have catalyzed the entire field—and the NCI now funds more than $150 million in pancreatic cancer research each year. But our work will not be done until we’ve conquered the disease. David Sabatini’s SLC38A9 study is the kind of intrepid and innovative research that, we believe, will get us to that goal.”