Molecular mechanisms of HER2-targeted therapy and strategies to overcome the drug resistance in colorectal cancer

• Published in: Biomedicine & pharmacotherapy Vol. 179; p. 117363
• Main Authors: Zhang, Rui, Su, Chang, Jia, Yongliang, Xing, Menglu, Jin, Shuiling, Zong, Hong
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-10-2024; Elsevier
• Subjects: Antibody-drug conjugates; Colorectal cancer; Drug resistance; HER2; Precision medicine; PR; IHC; TRAE; Colorectal cancer; Drug resistance; EGFR; ORR; DFS; SD; Precision medicine; mCRC; PD-L1; CTLA-4; PFS; ADCC; GEA; OS; BOR; PDX; TKIs; CMS; MSS; ADCs; TCGA; ISAC; Antibody-drug conjugates; DCR; CTC; FISH; NGS; HER2; PD-1; TLRs
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117363

HER2 amplification is one of the mechanisms that induce drug resistance to anti-EGFR therapy in colorectal cancer. In recent years, data from several randomized clinical trials show that anti-HER2 therapies improved the prognosis of patients with HER2-positive colorectal cancer. These results indicate that HER2 is a promising therapeutic target in advanced colorectal cancer. Despite the anti-HER2 therapies including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates improving the outcomes, less than 30 % of the patients achieve objective response and eventually have drug resistance. It is necessary to explore the primary and secondary mechanisms for the resistance to anti-HER2 therapies, which will pave the way to overcome the drug resistance. Several studies have reported the potential mechanisms for the resistance to anti-HER2 therapies. In this review, we present a comprehensive overview of the recent advances in clinical research, mechanisms of treatment resistance, and strategies for reversing resistance in HER2-positive colorectal cancer patients.