Breaking New Ground in Cancer Research

Cancer has many causes and many ways of growing and surviving, which enables the disease to show up in virtually every bodily tissue.

Elda Grabocka, PhD, assistant professor of cancer biology and surgery at Jefferson, is studying one of the key drivers of cancer: the oncogene, a class of genetic mutations that interrupt the body’s business as usual and create conditions for cancer to arise. Among the many oncogenic molecules is one called the KRAS gene, which is present in 30 percent of human cancers. Grabocka’s team focuses on KRAS as one of the main movers of pancreatic cancer, one of the most lethal cancers, because it is found in 95 percent of tumors for the disease.

The KRAS oncogene does many things within the body: it causes cells to grow out of control, makes them insensitive to cell death signals, increases their vascularization, and promotes metabolic changes. This oncogene also makes cells resistant to conventional therapeutic approaches and has earned the reputation of being “undruggable” because it has no accessible pockets for drugs to bind.

Grabocka’s team was the first to discover that cancer cells with oncogenic KRAS stimulate the formation of stress granules. Membraneless bundles of proteins and RNA (a kind of messenger DNA molecule), these organelles are created by healthy cells when confronted with cellular stresses like nutrient or oxygen deficiency and, in the case of cancer, chemo or radiation therapy.

Grabocka has found that stress granules, while not well understood, seem to function as a protective feature, preventing proteins and other signaling molecules from triggering cell death. In a healthy body, this is good, but when it comes to certain cancers, the process makes the disease remarkably resilient to many mainline therapies that work by stressing bodies at a cellular level.

The Grabocka Lab has continued to probe these molecular black boxes to find a way to reverse their effects and eventually make cancer cells more susceptible to stress and treatment. Their invaluable work could not continue without gifts from our grateful patients and benefactors. By supporting the lab, you can take part in one of the most important missions of our time: finding a cure for every cancer.