Existing cancer drugs could prove beneficial for more patients

Researchers discover additional targets for existing drugs used to treat a specific melanoma.

Existing cancer drugs could prove beneficial for more patients
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In a new study by the McGill University, scientists have found that a set of targeted cancer drugs, known as BRAF and MEK inhibitors, have turned out to be beneficial for some metastatic melanoma patients whose tumors incorporate a particular change in the BRAF gene, known as V600E. These drugs are also found to be effective for patients with other mutations in the BRAF gene, known as Class 2 BRAF Mutations.

Matthew Dankner, an MD/ Ph.D. student in Dr. Siegel’s lab and the lead author of the study said, “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. 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 Ph.D. 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 specialists became keen on investigating the capability of utilizing clinically affirmed BRAF and MEK inhibitors against melanomas with Class 2 BRAF mutations. This thought was first proposed when Dr. April Rose, the senior creator of the examination and a McGill Medicine graduate who finished 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 mind. Genomic analysis of the patient’s tumor uncovered a Class 2 BRAF mutation and a sample of the tissue was acquired by Dankner.

Dr. Rose said, “It all came together very quickly, within a couple of months working on this question, we knew we were on to something scientifically interesting and potentially very meaningful for patients.”

Dr. Siegel, Associate Professor in the Departments of Medicine, Biochemistry and Anatomy & Cell Biology at McGill’s Faculty of Medicine said, “The research serves as an important proof-of-principle study that indicates an existing treatment combination may represent an effective option for a new group of patients.

The next step in this work will be a clinical trial, which is currently being developed at the Princess Margaret Cancer Centre in Toronto, where Dr. Rose is now completing her residency in Medical Oncology. The trial will include patients with a number of different cancer types where Class 2 BRAF Mutations can be found, including melanoma and lung cancer.

The study is published in the journal Clinical Cancer Research.