Dr. Grabocka, assistant professor of Cancer Biology at the Sidney Kimmel Cancer Center at Jefferson, recently authored a study: “Mutant KRAS Enhances Tumor Cell Fitness by Upregulating Stress Granules. Grabocka and her colleagues found that the same signal that drives aggressive growth in a deadly cancer cell type also triggers coping mechanisms that make it “notoriously” hard to kill. The results of the study were published online in Cell.
Grabocka received her PhD in molecular pharmacology from Thomas Jefferson University in 2007 and returned home to Jefferson last April after working the last eight years as a postdoctoral scholar at NYU Langone Medical Center.
The study revolves around the gene KRAS, which when mutated drives abnormal growth in 90 percent of pancreatic cancers, as well as in many lung and julietta in canada colorectal tumors. When stressed, this cancer cell type — far more than most cancer cells — encases its genetic messages in protein globs called “stress granules” that lessen the effect of chemotherapies. As a second consequence of overactive KRAS, according to the study authors, cells harboring this mutation form many more stress-coping granules.
“This mechanism that we’re very excited about – the stress granules – is a way that KRAS cells can regulate the stress response, or how well the non-RAS cells cope with stress,” Dr. Grabocka said. “If we can block this, that’s a way to target the whole tumor, including other cancer cells that do not have a RAS mutation. Our goal is to understand the mechanism and what drives this on a molecular level so that the molecular targets that we identify can then be developed into therapies to target them.”
Dr. Grabocka, who designed the study while at NYU Langone, is thrilled to be back at Jefferson. She brings with her expertise on cell biology and molecular biology, having published numerous papers centered on elucidating dependencies of oncogenic KRAS cancers on tumorigenic stress adaptation mechanisms and their integration in therapeutic intervention modalities.
“I love the place and where it’s heading,” she said. “I can’t say enough good words about the Cancer Center and the Cancer Biology Department — I’ve never felt so much support.”
To read the entire study, click here.