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Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma. 2020
Hoi-Lam Ngan, and
Peony Hiu Yan Poon, and
Yu-Xiong Su, and
Jason Ying Kuen Chan, and
Kwok-Wai Lo, and
Chun Kit Yeung, and
Yuchen Liu, and
Eileen Wong, and
Hui Li, and
Chin Wang Lau, and
Wenying Piao, and
Vivian Wai Yan Lui
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong.
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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