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

Hoi-Lam NganPeony Hiu Yan PoonYu-Xiong SuJason Ying-Kuen ChanKwok-Wai LoChun Kit YeungYuchen LiuEileen WongHui LiChin Wang LauWenying PiaoVivian Wai Yan Lui

Published in: NPJ genomic medicine (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.

Keyphrases

signaling pathway
pi k akt
oxidative stress
advanced non small cell lung cancer
drug delivery
single cell
molecular docking
cancer therapy
high intensity
case control