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Whole-genome sequencing reveals complex mechanisms of intrinsic resistance to BRAF inhibition

2014; Elsevier BV; Volume: 25; Issue: 5 Linguagem: Inglês

10.1093/annonc/mdu049

1569-8041

Samra Turajlic, Simon J. Furney, Gordon Stamp, Sareena Rana, Gerda Ricken, Y. Oduko, G. Saturno, Caroline J. Springer, Andrew Hayes, Martin Gore, James Larkin, Richard Marais,

PI3K/AKT/mTOR signaling in cancer

BRAF is mutated in ∼42% of human melanomas (COSMIC. http://www.sanger.ac.uk/genetics/CGP/cosmic/) and pharmacological BRAF inhibitors such as vemurafenib and dabrafenib achieve dramatic responses in patients whose tumours harbour BRAF(V600) mutations. Objective responses occur in ∼50% of patients and disease stabilisation in a further ∼30%, but ∼20% of patients present primary or innate resistance and do not respond. Here, we investigated the underlying cause of treatment failure in a patient with BRAF mutant melanoma who presented primary resistance.