Melanoma Combination Therapy Resistance: What Lies Beneath?

According to a recent study, melanoma cells may become resistant to BRAF and MEK inhibitors after an initial tumor regression.

Results from the study, which was led by Roger Lo, MD, UCLA assistant professor of dermatology, and researchers from the UCLA Jonsson Comprehensive Cancer Center, were published in the journal Cancer Cell. Lo and his team analyzed a total of 43 melanoma patients’ tumor samples prior to treatment using BRAF/MEK inhibitors, but following a drug resistance-induced relapse.

Researchers were able to understand the mechanisms behind these cells’ drug resistance, through detailed genetic analyses within all tumor samples.

They noted that “resistance was acquired through the development of uncommon genetic modifications in a number of key cancer genes.” The discovery of these specific genetic alterations can uncover crucial information — researchers can determine not only which specific tumors had acquired drug resistance, but also could develop novel counteractive methods.

According to Lo, “We need to find ways to go beyond the BRAF+MEK drug combination, by possibly finding a third drug, or alter how we prescribe the combo of drugs. The idea is to eventually suppress melanoma drug resistance even before it arises.”

Antoni Ribas, MD, Professor of Hematology & Oncology, JCCC Member, and the study’s co-author, commented, “In most cases, melanoma eventually becomes resistant. We now understand the molecular basis of the resistance mechanisms, which leads to the planning of new treatment approaches to disable these mechanisms.”

The authors anticipated that the results from the new study will hopefully pave the way for a variety of efficient melanoma therapies. “If we understand how a disease fights your therapy, then we can start to design more effective treatment strategies,” said Lo.