KRAS Gene Presents Lung Cancer Treatment Target

Scientists discovered a new therapeutic target for lung cancer through the KRAS gene in a recent study published in Cell Reports.

While analyzing the underlying biology of the KRAS gene in lung cancer, researchers noted that activity from the Acyl-CoA synthetase long-chain family member 3 (ACSL3) gene is critical for cancerous cells to survive. They further found that by suppressing this gene, it causes lung cancer cell death.

Genetic mutations of KRAS occur in approximately 30% of lung cancer cases, and are associated with aggressive, chemo-resistant disease that has poor prognosis. According to the National Cancer Institute (NCI), lung cancer remains the leading cause of cancer-related deaths in the United States.

“Despite some recent advances, mutant KRAS a very challenging target,” said senior study author Pier Paolo Scaglioni. “There is a dearth of treatment options for tumors initiated by this gene. Mutant KRAS not only promotes the growth of tumors, but also the survival of established lung cancer. Since we have no clinically-relevant effective inhibitors of mutant KRAS at this time, there has been an intense clinical interest in developing a treatment that is proven effective.”

During the study, researchers used several complementary approaches, which included cell lines, mice, and human tumor samples, in order to gain a better understanding of the biological significance of ACSL3 in lung cancer.

The results of the study showed that the enzymatic activity of ACSL3 is imperative for the mutant KRAS gene to promote the formation of lung cancer, and the critical role that fatty acids play in the disease.

“There is an urgent need for discovery of additional targets that inhibit lipid metabolism in cancer cells that could lead to targeted therapies: the discovery of the importance of ACSL3 in lung cancer meets this unmet need,” said first study author Mahesh S. Padanad.