A set of targeted cancer drugs, known as BRAF and MEK inhibitors, have proven to be beneficial for some metastatic melanoma patients whose tumors include a specific mutation in the BRAF gene, known as V600E. A recent study conducted in the lab of Dr. Peter Siegel at McGill University’s Goodman Cancer Research Centre suggests that these same drugs may prove beneficial for a broader range of cancer patients.

The results of the study, published in the journal Clinical Cancer Research, show that these drugs may also be effective for patients with other mutations in the BRAF gene, known as class 2 BRAF mutations. At the moment, melanoma and lung cancer patients diagnosed with class 2 BRAF mutant tumors have no targeted therapy options available. This leaves these patients with only chemotherapy or drugs known as checkpoint inhibitor immunotherapy, which block proteins that prevent one’s own immune system from attacking cancer cells.

“Checkpoint inhibitor immunotherapy has dramatically improved the outlook for metastatic melanoma and lung cancer patients as a whole, but unfortunately only up to half of all patients treated with these drugs benefit,” explains Matthew Dankner, an MD/PhD student in Dr. Siegel’s lab and the lead author of the study.“Our results point to a viable second-line alternative for these patients in the form of targeted therapy drugs that are taken in pill form, tend to be well-tolerated by patients, and have the potential to improve survival and quality of life.”

The researchers became interested in exploring the potential of using clinically approved BRAF and MEK inhibitors against melanomas with class 2 BRAF mutations. This idea was first proposed when Dr. April Rose, the senior author of the study and a McGill Medicine graduate who completed her PhD in Dr. Siegel’s lab, saw a patient with Dr. Catalin Mihalcioiu at the MUHC Oncology Clinic whose metastatic melanoma had spread to the brain. Genomic analysis of the patient’s tumor revealed a class 2 BRAF mutation and a sample of the tissue was obtained by Dankner.

The researchers then used the melanoma tissue to create a unique mouse model of human cancer. These patient-derived mouse tumors, containing class 2 BRAF mutations, were treated with the BRAF and MEK inhibitors and the tumors shrunk. The researchers then tested the drugs on melanoma cells derived from several additional patients with class 2 BRAF mutations, and observed the same results. “It all came together very quickly,” recounts Dr. Rose, “within a couple of months working on this question, we knew we were on to something scientifically interesting and potentially very meaningful for patients.”