Genetic alterations of the KRAS gene are some of the most common mutations in lung cancer patients, but unfortunately these patients have few effective treatment options. Drugs that target the G12C mutation in KRAS have shown some activity in lung cancer; however, alternative signaling pathways are often activated that bypass the KRAS inhibitor, resulting in drug resistance. In a new article published in Clinical Cancer Research, Moffitt Cancer Center researchers show that various subtypes of lung cancer cells activate different signaling pathways in response to KRASG12C inhibitor treatment. These results may help identify potential combination therapy approaches and guide treatment decisions for lung cancer patients in the future.
The G12C mutation of KRAS occurs in approximately 16% of lung adenocarcinomas. Several drugs that target this specific mutation are in clinical development and have shown activity in some lung cancer patients, but these drugs are less effective in certain patients. As a result, combination treatment with other targeted agents may be necessary to see a benefit, but it is not clear which combination treatment strategies would work best.