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Two groups of investigators have made progress in the search for targetable changes in melanomas that have acquired resistance to BRAF inhibitors (BRAFi), identifying one such target.
Miao and colleagues generated melanoma cell lines that acquired resistance to vemurafenib and found that the kinase EphA2 had significantly increased expression in a subset of cell lines. In matched patient samples of melanoma taken prior to treatment with BRAFi and MEK inhibitors (MEKi) and postrelapse, EphA2 expression was increased after relapse. Suppression of EphA2 expression restored sensitivity to vemurafenib. The authors then generated a first-in-class small-molecule inhibitor of EphA2 and demonstrated that it could both restore the sensitivity of vemur…