Although one of the most commonly mutated genes in human cancer, the KRAS gene has proven difficult to successfully target. A recent study published in Cell Reports has highlighted a potential new way of targeting this genetic aberration in KRAS-driven lung cancer.
The investigating team from UT Southewestern Medical Center (TX, USA) observed the biology of KRAS in lung cancer and determined that activity of the ACSL3 gene is critical for survival of malignant cells. Subsequently, they determined that suppression of ACSL3 resulted in cancer cell death.
Mutations in the KRAS gene are found in approximately 30% of all lung cancer cases and are associated with aggressive, therapy-resistant disease with a poor prognosis.
“Despite some recent advances, mutant KRAS remains a very challenging target. There is a dearth of treatment options for tumors initiated by this gene,” commented senior author Pier Paolo Scaglioni of the Harold C. Simmons Comprehensive Cancer Center at Southwestern.
Using cell lines, mice, and human patient tumor samples, the team found that the enzymatic activity of ACSL3 is needed for the mutant KRAS gene to promote the formation of lung cancer, and further demonstrated that fatty acids, which are the substrates of ACSL3 enzyme, play a critical role in lung cancer.
“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,” reported Mahesh S Padanad, first author from UT Southwestern.