@article{94f05c6a0fd3409ead52e3aaf6785cd0,
title = "Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma",
abstract = "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{\textquoteright}s effect is moderate.",
author = "Ngan, {Hoi Lam} and Poon, {Peony Hiu Yan} and Su, {Yu Xiong} and Chan, {Jason Ying Kuen} and Lo, {Kwok Wai} and Yeung, {Chun Kit} and Yuchen Liu and Eileen Wong and Hui Li and Lau, {Chin Wang} and Wenying Piao and Lui, {Vivian Wai Yan}",
note = "Funding Information: This research is funded by the General Research Fund (#17114814 to V.W.Y.L., Research Grant Council, Hong Kong), and V.W.Y.L. also receives fundings from the Research Grant Council, General Research Fund—17114814, 17121616, 14168517, and R4017-18; Research Impact Fund; the Health and Medical Research Fund (HMRF#15160691, the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region); University-Industry Collaboration Program (UIM/329; Innovation and Technology Fund, Hong Kong government, Hong Kong SAR and Lee{\textquoteright}s Pharmaceutical (HK) Limited); the Hong Kong Cancer Fund, Hong Kong SAR; Start-up Fund from the School of Biomedical Sciences, Faculty of Medicine, CUHK; and 1R01CA229836-01A1 (as Co-Investigator) from the National Cancer Institute, NIH, USA. Y.L. and W.P. receive funding supports (Postdoctoral Hub PH-ITF Ref.: PiH/052/18 and PiH/234/18 of UIM/ 329) from the Innovation and Technology Fund, Hong Kong government. J.Y.K.C. receives funding support by the Dr. Stanley Ho Medical Foundation and the General Research Fund (#14109716; #14108818 General Research Fund, Research Grant Council, Hong Kong government, Hong Kong SAR). Y.-X.S. receives funding support from HK RGC-GRF #17120718. Funding Information: All authors do not have any conflicts of interest directly related to this study. For fundings unrelated to this study, V.W.Y.L. receives funding from the Hong Kong Cancer Fund, Hong Kong SAR on an ovarian cancer study. V.W.Y.L. served as a consultant for Novartis Pharmaceuticals (HK) Ltd. in 2015–2016. Y.L., W.P. and E.W. receive funding supports (Postdoctoral Hub PH-ITF Ref.: PiH/052/18 and PiH/234/18 of UIM/329) from the Innovation and Technology Fund, Hong Kong government on an unrelated study in head and neck cancer. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41525-020-0124-5",
language = "English (US)",
volume = "5",
journal = "npj Genomic Medicine",
issn = "2056-7944",
publisher = "Nature Publishing Group",
number = "1",
}