Erlotinib sensitivity of MAPK1 p.D321N mutation in head and neck squamous cell carcinoma

Hoi-Lam Ngan; Peony Hiu Yan Poon; Yu-Xiong Su; Jason Ying Kuen Chan; Kwok-Wai Lo; Chun Kit Yeung; Yuchen Liu; Eileen Wong; Hui Li; Chin Wang Lau; Wenying Piao; Vivian Wai Yan Lui

doi:10.1038/s41525-020-0124-5

Erlotinib sensitivity of MAPK1 p.D321N mutation in head and neck squamous cell carcinoma

NPJ Genom Med. 2020 Apr 20;5(1):17. doi: 10.1038/s41525-020-0124-5. eCollection 2020.

Authors

Affiliations

¹ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong.
² 2Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Hong Kong.
³ Department of Otorhinolaryngology, Head & Neck Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong.
⁴ Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong.
⁵ 5Department of Otorhinolaryngology Head and Neck, Yan Chai Hospital, Hong Kong SAR, Hong Kong.

^# Contributed equally.

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's effect is moderate.

Keywords: Cancer genetics; Head and neck cancer; Targeted therapies.

Abstract

Grants and funding