Format

Send to

Choose Destination
Pharmacol Ther. 2019 Jul;199:188-196. doi: 10.1016/j.pharmthera.2019.03.010. Epub 2019 Apr 2.

Prevalence and role of HER2 mutations in cancer.

Author information

1
Human Oncology & Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, United States of America; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro 88100, Italy.
3
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, United States of America. Electronic address: alessandro.santin@yale.edu.
4
Human Oncology & Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: scaltrim@mskcc.org.

Abstract

HER2 activating mutations act as oncogenic drivers in various cancer types. In the clinic, they can be identified by next generation sequencing (NGS) in either tumor biopsies or circulating cell-free DNA (cfDNA). Preclinical data indicate that HER2 "hot spot" mutations are constitutively active, have transforming capacity in vitro and in vivo and show variable sensitivity to anti-HER2 based therapies. Recent clinical trials also revealed activity of HER2-targeted drugs against a variety of tumors harboring HER2 mutations. Here, we review the prevalence and type of HER2 mutations identified in different human cancers, their biochemical and biological characterization, and their sensitivity to anti HER2-based therapies in both preclinical and clinical settings.

KEYWORDS:

Afatinib; HER2 mutations; Neratinib; Next-generation sequencing (NGS); TCGA

PMID:
30951733
PMCID:
PMC6571037
[Available on 2020-07-01]
DOI:
10.1016/j.pharmthera.2019.03.010

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center