TAMPA, Fla. (Jan. 31, 2025) — 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.
This study was supported by the National Institutes of Health (UH3CA202970 and P30CA076292), the Moffitt Lung Cancer Center of Excellence and Revolution Medicines.
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 57 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter, Instagram and YouTube.
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Journal
Clinical Cancer Research
Method of Research
Observational study
Subject of Research
Cells
Article Title
In situ RAS:RAF binding correlates with response to KRASG12C inhibitors in KRASG12C-mutant non–small cell lung cancer
Article Publication Date
21-Jan-2025