Emergence of ERBB2 Mutation as a Biomarker and an Actionable Target in Solid Cancers

AbstractThe oncogenic role ERBB2 amplification is well established in breast and gastric cancers. This has led to the development of a well‐known portfolio of monoclonal antibodies and kinase inhibitors targeting the ERBB2 kinase. More recently, activating mutations in the ERBB2 gene have been increasingly reported in multiple solid cancers and were shown to play an oncogenic role similar to that of ERBB2 amplification. Thus, ERBB2 mutations define a distinct molecular subtype of solid tumors and serve as actionable targets. However, efforts to target ERBB2 mutation has met with limited clinical success, possibly because of their low frequency, inadequate understanding of the biological activity of these mutations, and difficulty in separating the drivers from the passenger mutations. Given the current impetus to deliver molecularly targeted treatments for cancer, there is an important need to understand the therapeutic potential of ERBB2 mutations. Here we review the distribution of ERBB2 mutations in different tumor types, their potential as a novel biomarker that defines new subsets in many cancers, and current data on preclinical and clinical efforts to target these mutations.Implications for Practice.A current trend in oncology is to identify novel genomic drivers of solid tumors and developing precision treatments that target them. ERBB2 amplification is an established therapeutic target in breast and gastric cancers, but efforts to translate this finding to other sol...

Source: The Oncologist - December 9, 2019 Category: Cancer & Oncology Authors: Janakiraman Subramanian, Archana Katta, Ashiq Masood, Dashavantha Reddy Vudem, Rama Krishna Kancha Tags: Review, Precision Medicine Clinic: Molecular Tumor Board, Cancer Diagnostics and Molecular Pathology Source Type: research