Biomarker predicts KRASG12C inhibitor success in lung cancer treatment

A new study from Moffitt Cancer Center could help doctors predict how well patients with a specific type of lung cancer will respond to new therapies. The research, published in Clinical Cancer Research, found that measuring the interaction between two proteins, RAS and RAF, could provide valuable insights into the effectiveness of treatments for patients with KRASG12C-mutant non-small cell lung cancer, a type of lung cancer known for being particularly difficult to treat.

The findings revealed that tumors with higher levels of RAS–RAF protein interaction were more likely to respond to KRASG12C inhibitors, a class of drugs designed to target the KRASG12C mutation. This discovery could help doctors identify which patients are most likely to benefit from this treatment.

The researchers developed a special test, called a proximity ligation assay, to measure how often RAS and RAF interact inside cancer cells. Their results showed that tumors with stronger RAS–RAF interactions also had higher levels of active RAS signaling, which is linked to better responses to KRASG12C inhibitors.

“Our findings could be a game-changer for treating KRASG12C-mutant NSCLC,” said Ryoji Kato, Ph.D., a postdoctoral fellow in the lab of Eric Haura, M.D. “By measuring RAS–RAF interactions, we can potentially help doctors make more informed decisions and provide better treatment outcomes for patients.”

The study also compared this method with other common markers of cancer activity, like EGFR, and found that EGFR activity did not predict response to the KRASG12C inhibitors. This suggests that RAS–RAF interaction is a more accurate biomarker for treatment response.

“This research opens the door to more personalized cancer treatment,” said Haura, associate center director for Clinical Science at Moffitt. “The ability to assess RAS signaling directly in tumor samples could lead to more targeted therapies and better outcomes for patients with KRAS-mutant cancers.”

The new proximity ligation assay method could become an important tool in clinical settings, helping doctors select the right treatments for the right patients and improving outcomes in a type of cancer that has few effective treatment options.