Researchers have uncovered a novel combination therapy leveraging the U.S. Food and Drug Administration (FDA)-approved KRAS inhibitor sotorasib and an experimental drug called FGTI-2734, which could improve the efficacy of precision medicine in patients with KRAS-mutated non–small cell lung cancer (NSCLC), according to a recent study published by Kazi et al in the Journal of Thoracic Oncology.
Background
KRAS G12C mutations are a driver in about 14% of NSCLC cases.
Although the FDA-approved drugs sotorasib and adagrasib have provided hope to some patients by targeting KRAS G12C, the majority of tumors either resist treatment from the start or relapse within months.
Study Methods and Results
In the study, the researchers sought to understand the benefit of combining sotorasib with FGTI-2734, which was designed to block cancer cells’ wild type RAS membrane localization. The experimental drug is also capable of prohibiting a cellular process known as ERK reactivation—where ERK belongs to a family of enzymes regulating communication within cells. Cancer cells use ERK reactivation to escape sotorasib treatment.
The researchers discovered that the combination of sotorasib plus FGTI-2734 successfully prevented the cancer’s ability to develop treatment resistance.
“This could be a paradigm shift in how we treat lung cancer,” highlighted senior study author Said M. Sebti, PhD, Professor in the Department of Pharmacology and Toxicology at the School of Medicine as well as Associate Director for Basic Research and the Lacy Family Chair in Cancer Research at the Massey Comprehensive Cancer Center at the Virginia Commonwealth University. “We’re hoping to give patients a fighting chance against resistance,” he added.
Conclusions
While the results were observed in laboratory studies using patient-derived tumors, the researchers are currently working toward securing FDA approval for clinical trials—a crucial step toward bringing the innovation to patients.
“Every researcher’s dream in this noble field of research is to have a real impact on patients [with cancer],” Dr. Sebti emphasized. “This discovery may realize this dream by eventually leading to better outcomes and longer lives for [patients] facing lung cancer,” he concluded.
Disclosure: For full disclosures of the study authors, visit jto.org.
