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SALT LAKE CITY, UT – A breakthrough in melanoma treatment may be on the horizon, as researchers at Huntsman Cancer Institute at the University of Utah have discovered a promising new oral drug therapy combination. This combination shows potential in not only treating advanced melanoma but also preventing its spread to the brain, a major cause of death in melanoma patients.
The research, published in the journal Cell Reports Medicine, was led by Sheri Holmen, Ph.D., who emphasized the urgent need for effective treatments for melanoma that has metastasized to the brain. “Once melanoma has spread to the brain, it’s very hard to treat,” Holmen stated. “We wanted to find a solution to an unmet clinical need for those patients who had no other treatment options available, and this is a huge step forward.”
The team identified focal adhesion kinase (FAK), an enzyme regulating cell growth, as a key factor in melanoma metastasis. By inhibiting FAK in combination with RAF and MEK inhibitors, which target another cellular pathway involved in cancer cell growth, they observed significantly prolonged survival rates in preclinical mouse models. This combination specifically targeted melanoma driven by a BRAF gene mutation, found in approximately 50% of metastatic melanoma patients.
Crucially, the oral drug combination, consisting of defactinib (FAK inhibitor) and avutometinib (RAF/MEK inhibitor), demonstrated the ability to both treat existing brain metastases and prevent their development. “This combination drug therapy also stopped the development of brain metastasis, and that’s where this research is very exciting,” Holmen explained.
The oral administration of this therapy offers a significant advantage, particularly for patients in rural areas who face challenges accessing traditional infusion treatments like immunotherapy. “Having oral drugs available will increase treatment options for our patients, especially those living in rural and frontier areas,” Holmen noted.
The research has now progressed to clinical trials at Huntsman Cancer Institute and Holden Comprehensive Cancer Center at the University of Iowa, led by Howard Colman, MD, Ph.D. The trials are open to patients with melanoma with brain metastases.
Disclaimer: It is important to note that this research is based on preclinical and early clinical trial data. While the results are promising, further clinical trials are necessary to confirm the safety and efficacy of this drug combination in a larger patient population. This news article is for informational purposes only and should not be interpreted as medical advice. Patients should consult with their healthcare providers to discuss appropriate treatment options.
More information: Jared Almazan et al, Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases, Cell Reports Medicine (2025). DOI: 10.1016/j.xcrm.2025.101943
