TY - JOUR
T1 - Precision drugging of the MAPK pathway in head and neck cancer
AU - Ngan, Hoi Lam
AU - Law, Chun Ho
AU - Choi, Yannie Chung Yan
AU - Chan, Jenny Yu Sum
AU - Lui, Vivian Wai Yan
N1 - Funding Information:
This study was supported by the Start-up fund from Georgia Cancer Center, Medical College of Georgia, Augusta University, USA (to V.W.Y.L), and Research Impact Fund (R4015-19F in the period of 6/29/2020-9/7/2021) from the Research Grants Council, University Grants Committee, Hong Kong Government, Hong Kong SAR.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The mitogen-activating protein kinase (MAPK) pathway is central for cell proliferation, differentiation, and senescence. In human, germline defects of the pathway contribute to developmental and congenital head and neck disorders. Nearly 1/5 of head and neck squamous cell carcinoma (HNSCC) harbors MAPK pathway mutations, which are largely activating mutations. Yet, previous approaches targeting the MAPK pathway in HNSCC were futile. Most recent clinical evidences reveal remarkable, or even exceptional pharmacologic vulnerabilities of MAPK1-mutated, HRAS-mutated, KRAS-germline altered, as well as BRAF-mutated HNSCC patients with various targeted therapies, uncovering diverse opportunities for precision drugging this pathway at multiple “genetically condemned” nodes. Further, recent patient tumor omics unveil novel effects of MAPK aberrations on direct induction of CD8+ T cell recruitment into the HNSCC microenvironment, providing evidences for future investigation of precision immunotherapy for this large subset of patients. MAPK pathway-mutated HNSCC should warrant precision therapy assessments in vigorous manners.
AB - The mitogen-activating protein kinase (MAPK) pathway is central for cell proliferation, differentiation, and senescence. In human, germline defects of the pathway contribute to developmental and congenital head and neck disorders. Nearly 1/5 of head and neck squamous cell carcinoma (HNSCC) harbors MAPK pathway mutations, which are largely activating mutations. Yet, previous approaches targeting the MAPK pathway in HNSCC were futile. Most recent clinical evidences reveal remarkable, or even exceptional pharmacologic vulnerabilities of MAPK1-mutated, HRAS-mutated, KRAS-germline altered, as well as BRAF-mutated HNSCC patients with various targeted therapies, uncovering diverse opportunities for precision drugging this pathway at multiple “genetically condemned” nodes. Further, recent patient tumor omics unveil novel effects of MAPK aberrations on direct induction of CD8+ T cell recruitment into the HNSCC microenvironment, providing evidences for future investigation of precision immunotherapy for this large subset of patients. MAPK pathway-mutated HNSCC should warrant precision therapy assessments in vigorous manners.
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U2 - 10.1038/s41525-022-00293-1
DO - 10.1038/s41525-022-00293-1
M3 - Review article
AN - SCOPUS:85126719497
SN - 2056-7944
VL - 7
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 20
ER -