Researchers may have uncovered a novel strategy to help predict how well patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC) will respond to new therapies, according to a recent study published by Kato et al in Clinical Cancer Research.
Study Methods and Results
Researchers developed a proximity ligation assay to measure how often RAS and RAF proteins interacted inside cancer cells, and discovered that measuring this interaction could provide valuable insights into the effectiveness of treatments in patients with KRAS G12C–mutated NSCLC. For instance, tumors with stronger RAS-RAF protein interactions had higher levels of active RAS signaling and were more likely to respond to KRAS G12C inhibitors.
The researchers also compared their novel method with other common markers of cancer activity, like EGFR. They found that EGFR activity was not predictive of response to KRAS G12C inhibitors, suggesting that RAS-RAF interactions could serve as a more accurate biomarker for treatment response.
Conclusions
The findings could help physicians identify which patients may be most likely to benefit from KRAS G12C inhibitors.
“Our findings could be a game-changer for treating KRAS G12C–[mutated] NSCLC. By measuring RAS-RAF interactions, we can potentially help [physicians] make more informed decisions and provide better treatment outcomes for patients,” emphasized lead study author Ryoji Kato, PhD, a postdoctoral fellow at the Moffitt Cancer Center.
The new proximity ligation assay method could become an important tool in clinical settings, helping physicians select the most effective treatments and improving outcomes in KRAS G12C–mutated NSCLC.
“This research opens the door to more personalized cancer treatment,” underscored senior study author Eric Haura, MD, Associate Center Director for Clinical Science at the Moffitt Cancer Center. “The ability to assess RAS signaling directly in tumor samples could lead to more targeted therapies and better outcomes for patients with KRAS-[mutated] cancers,” he concluded.
Disclosure: The research in this study was supported by the National Institutes of Health, the Moffitt Lung Cancer Center of Excellence, and Revolution Medicines. For full disclosures of the study authors, visit aacrjournals.org.
