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Significance Preclinical studies of metastatic melanoma treated with targeted therapeutics have suggested that alternating periods of treatment and withdrawal might delay the onset of resistance. This has been attributed to… Click to show full abstract
Significance Preclinical studies of metastatic melanoma treated with targeted therapeutics have suggested that alternating periods of treatment and withdrawal might delay the onset of resistance. This has been attributed to drug addiction, where cells lose fitness upon drug removal due to the resulting hyperactivation of mitogen-activated protein (MAP) kinase signaling. This study presents evidence that the intermittent treatment response can also be explained by the resensitization of cells following drug removal and enhanced cell loss upon drug rechallenge. Resensitization is accompanied by adaptive transcriptomic switching and occurs despite the sustained expression of resistance genes throughout the intermittent treatment.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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