Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and d...

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Detalles Bibliográficos
Autores principales: Ngan, Hoi-Lam, Poon, Peony Hiu Yan, Su, Yu-Xiong, Chan, Jason Ying Kuen, Lo, Kwok-Wai, Yeung, Chun Kit, Liu, Yuchen, Wong, Eileen, Li, Hui, Lau, Chin Wang, Piao, Wenying, Lui, Vivian Wai Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171136/
https://www.ncbi.nlm.nih.gov/pubmed/32351709
http://dx.doi.org/10.1038/s41525-020-0124-5
Descripción
Sumario:Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated MAPK1 mutations. Residues D321, R135, and E322 are in 3D proximity. MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K’s effect is moderate.

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