Thomas Jefferson University researchers found that mice with non-small cell lung cancer with KRAS-related gene mutations benefit from therapy with two experimental drugs, trametinib and palbociclib, along with radiation therapy.
The research paper, titled “Coadministration of Trametinib and Palbociclib Radiosensitizes KRAS-Mutant Non-Small Cell Lung Cancers In Vitro and In Vivo,” was published in Clinical Cancer Research.
According to the American Cancer Society, 85 percent to 90 percent of lung cancers are considered non-small cell lung cancer (NSCLC). Treatment success varies greatly with the type of mutation observed in the cancer, and certain cancer subtypes, such as those harboring mutations in the KRAS gene, are still resistant to standard and targeted therapies.
Researchers who analyzed a KRAS-mutant subset in NSCLC cells observed that some cells were sensitive while others were resistant to a drug that targeted the KRAS gene pathway. The resistant subtype of cells was found to have an additional mutation in a protein called p16. The presence of this mutation, according to a lung-cancer patient genotype database, is associated with lower overall survival rates.
To overcome this added resistance, researchers combined a KRAS-targeting drug with another drug that would mitigate the effects of the p16 mutation. Furthermore, this combination made the resistant cancer cells susceptible to radiation treatment.
The two drugs, trametinib and palbociclib, are not approved to treat lung cancer but are currently in an ongoing clinical trial for combination treatment of patients with solid tumors and melanoma.
“Although further research in human subjects is needed to confirm the finding, our study suggests that we may be able to identify non-small cell lung cancer patients who are likely to benefit most from this combination of therapies,” Dr. Bo Lu, M.D., Ph.D., and professor of radiation oncology, said in a press release, adding, “If you hit one target, another can take over. If you hit two, it becomes a lethal bullet.”
Such findings might represent a novel therapeutic strategy for patients with advanced KRAS-mutant NSCLCs.