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.


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.