Molecular Clues to Skin Cancer

In recent years, targeted therapy using BRAF inhibitors has substantially improved survival rates for patients with advanced melanoma. However, the majority of patients eventually become resistant to therapy and the result: treatment cessation. Now, researchers from California, USA, have shed light on a gene that could potentially provide a solution to the problem of BRAF inhibitor resistance, and play an important role in melanoma progression.

“Our broad-based goal is to understand factors that mediate melanoma progression, in the hope of developing markers that predict melanoma metastasis, or that may serve as targets for therapy of metastatic melanoma,” says co-author of the study (1), Mohammed Kashani-Sabet. “We found that the bromodomain PHD finger transcription factor (BPTF) gene plays an important role in melanoma progression, and that higher levels of BPTF expression in melanoma cells promoted resistance to BRAF-targeted therapies,” he explains.

Kashani and his team are hopeful their discovery will impact the diagnosis and treatment of melanoma, as BPTF may prove to be an important molecular marker for diagnosis and prognosis of cancer. Further, they have shown it to play a role in activation of the MAP kinase pathway, which is key for melanoma proliferation, and an important therapeutic target along with BRAF inhibition. A future strategy for preventing resistance to treatment could involve teaming BRAF inhibitors with a therapy that targets the resistance mechanisms, suggests Kashani.

“This discovery may give pathologists an additional tool to assess melanoma diagnosis and prognosis, and a marker to allow identification of patients in whom treatment with BRAF inhibitors can be continued”, says Kashani. “In the future, we aim to gain further understanding of the role of BPTF in tumor progression, and develop it as a target for cancer therapy,” he concludes.