Study Reveals Mechanisms Behind Melanoma Combination Therapy Resistance

Study Reveals Mechanisms Behind Melanoma Combination Therapy Resistance

shutterstock_104107130Researchers from the UCLA Jonsson Comprehensive Cancer Center have published their latest results in the journal Cancer Cell, whereby they reveal how melanoma cells can become resistant to BRAF and MEK inhibitors after initial tumor regression.

The research team, led by Dr. Roger Lo, analyzed 43 tumor samples from melanoma patients before treatment with BRAF/MEK inhibitors and after relapse due to drug resistance.

A significant percentage of all melanoma cases (50%) carry a BRAF protein mutation, and one of the commonly used treatments for patients diagnosed with BRAF V600 mutation-positive melanoma with advanced stage disease includes selective BRAF inhibitor with or without a MEK inhibitor.

A thorough genetic analysis was preformed in all tumor samples, allowing researchers to understand the mechanisms behind these cells’ drug resistance.

Dr. Lo and his team found that resistance is acquired through the development of uncommon genetic modifications in a number of key cancer genes.

The discovery of these specific genetic alterations can reveal which tumors have acquired drug resistance but can also allow the development of novel ways to counteract them.

“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,” Dr. Lo, UCLA assistant professor of dermatology, said in a news release. “The idea is to eventual suppress melanoma drug resistance even before it arises.”

“In most cases, melanoma eventually becomes resistant,” added Dr. Antoni Ribas, JCCC member and professor of hematology and oncology, and a co-author of the study. “We now understand the molecular basis of the resistance mechanisms, which leads to the planning of new treatment approaches to disable these mechanisms.”

Dr. Lo and Dr. Ribas had already worked together to understand how melanoma cells gained resistance to Zelboraf (vemurafenib), with results from these earlier studies proving invaluable to develop new combination therapies for melanoma using BRAF and MEK inhibitors.

The results from this new study will hopefully lead to more efficient therapies for melanoma patients.

“If we understand how a disease fights your therapy, then we can start to design more effective treatment strategies,” Dr. Lo concluded.

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