Xiangju Kong

TL;DR: It is found that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2, suggesting that attenuating the biological processes that underlie IPRES may improve anti-PD-1 response in melanoma and other cancer types.

TL;DR: Acquired resistance to PD-1 blockade immunotherapy in patients with melanoma was associated with defects in the pathways involved in interferon-receptor signaling and in antigen presentation.

TL;DR: It is shown that melanomas escape B-RAF(V600E) targeting not through secondary B-RF(V 600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies.

TL;DR: The model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS–GTP too low to support RAF dimerization is supported and a novel mechanism of acquired resistance in patients is identified: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.

TL;DR: In this article, the authors performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib.