Open AccessMechanisms of neratinib resistance in HER2-mutant metastatic breast cancer
Author(s) -
Lisa D. Eli,
Shyam M. Kavuri
Publication year - 2022
Publication title -
cancer drug resistance
Language(s) - English
Resource type - Journals
ISSN - 2578-532X
DOI - 10.20517/cdr.2022.48
Subject(s) - neratinib , breast cancer , metastatic breast cancer , medicine , cancer research , oncology , acquired resistance , drug resistance , epidermal growth factor receptor , cancer , clinical trial , trastuzumab , lapatinib , biology , genetics
Human epidermal growth factor receptor 2 (HER2) is a major drug target and clinical biomarker in breast cancer treatment. Targeting HER2 gene amplification is one of the greatest successes in oncology, resulting in the use of a wide array of HER2-directed agents in the clinic. The discovery of HER2 -activating mutations as novel therapeutic targets in breast and other cancers marked a significant advance in the field, which led to the metastatic breast and other solid tumor trials MutHER (NCT01670877), SUMMIT (NCT01953926), and one arm of plasmaMATCH (NCT03182634). These trials reported initial clinical benefit followed by eventual relapse ascribed to either primary or acquired resistance. These resistance mechanisms are mediated by additional secondary genomic alterations within HER2 itself and via hyperactivation of oncogenic signaling within the downstream signaling axis.