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Therapeutic resistance

Multiple mechanisms to keep going

Nature Reviews Cancer volume 15, page 635 (2015)Cite this article

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the landscape of acquired resistance to MAPK pathway inhibitors

Hugo, Shi, Sun, Piva et al. used a cohort of 67 human melanomas with matched pretreatment samples and samples taken at disease progression while on therapy (either a BRAFi or a BRAFi plus MEKi). Comparison of whole-exome sequencing of the resistant samples with that of matched pretreatment samples revealed mutations in several MAPK and PI3K pathway genes. Mutations in NRAS, KRAS and BRAF were the most common MAPKi resistance-associated genetic alterations. However, 26 of the melanomas had no genetic mechanism of acquired resistance, indicating that non-genetic events could account for MAPKi resistance in these tumours.

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References

  1. Hugo, W., Shi, H., Sun, L., Piva, M. et al. Non-genomic and immune evolution of melanoma acquiring MAPKi resistance. Cell 162, 1271–1285 (2015)

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  1. Gemma K. Alderton
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Alderton, G. Multiple mechanisms to keep going. Nat Rev Cancer 15, 635 (2015). https://doi.org/10.1038/nrc4034

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