Heterogeneous clinical and pathological landscapes of HER2 positive colorectal cancer

Abstract

ABSTRACT Introduction: Metastatic (m) colorectal cancer (CRC) can be divided into specific subgroups under the ‘one gene, one drug’ paradigm of precision medicine. Progress of targeted therapy in mCRC patients significantly improved the overall survival rate, notably by therapy targeting of EGFR signaling in RAS wild-type mCRC patients. Activation of the HER2 pathway is an important mechanism of resistance for anti-EGFR therapy. Area covered: Inhibition of HER2 with monoclonal antibodies and/or tyrosine kinase inhibitors induces tumor responses in partial HER2-positive CRC refractory to standard systemic therapy. This manuscript aimed to provide an overall insight of the HER2 expression pattern and highlighted specific clinicopathological and molecular features involved in mCRC. In addition, we summarize preclinical and clinical trials in HER2-positive mCRC. Expert opinion: The status and progression of HER2-positive gastric cancer and breast cancer and anti-HER2 therapy have been reported widely. However, the understanding of HER2-positive CRC models which may guide future therapeutic decision-making is poor. Therefore, it is essential to summarize the existing research to extract similarity and difference among various studies.