Ado-tratuzumab emtansine beyond breast cancer: therapeutic role of targeting other HER2-positive cancers

Abstract

Ado-trastuzumab emtansine (T-DM1) is an antibody–drug conjugate approved by the FDA in 2013 for advanced HER2-positive breast cancer treatment exhibiting promising clinical benefits. However, HER2 overexpression and gene amplification have also been reported in other cancers like gastric cancer, non-small cell lung cancer (NSCLC), and colorectal cancer. Numerous preclinical studies have also revealed the significant antitumor effect of T-DM1 on HER2-positive tumors. With the advancement in research, several clinical trials have been conducted to investigate the antitumor effect of T-DM1. In this review, we briefly introduced the pharmacological effects of T-DM1. We reviewed its preclinical and clinical studies, especially on other HER2-positive cancers, establishing what has been encountered between its preclinical and clinical studies. In clinical studies, we found that T-DM1 has a therapeutic value on other cancers. An insignificant effect was observed on gastric cancer and NSCLC, inconsistent with the preclinical studies.

Antitumor activities against breast cancers by an afucosylated anti‐HER2 monoclonal antibody H2Mab‐77‐mG2a‐f

“…T‐DM1 was authorized for HER2‐positive advanced breast cancer by the US Food and Drug Administration (FDA) and the European Medicines Agency in 2013, while T‐DXd was approved in the United States in 2019 for HER2‐positive metastatic or unresectable breast cancer. 21 , 22 , 23 Trastuzumab binds to HER2 domain IV, causing antibody‐dependent cellular cytotoxicity (ADCC) and antibody‐dependent cell phagocytosis. 24 , 25 , 26 The extracellular domain of HER2 has been seen in breast cancer patients' serum, but trastuzumab binding prevents this HER2 cleavage.…”

“…Trastuzumab has been used to treat HER2‐positive metastatic breast cancer. T‐DM1 was authorized for HER2‐positive advanced breast cancer by the US Food and Drug Administration (FDA) and the European Medicines Agency in 2013, while T‐DXd was approved in the United States in 2019 for HER2‐positive metastatic or unresectable breast cancer 21–23 . Trastuzumab binds to HER2 domain IV, causing antibody‐dependent cellular cytotoxicity (ADCC) and antibody‐dependent cell phagocytosis 24–26 .…”

Antitumor Activities against Breast Cancers by an Afucosylated Anti-HER2 Monoclonal Antibody H₂Mab-77-mG_2a-f

“…Trastuzumab has been used to treat HER2-positive metastatic breast cancer. T-DM1 was authorized for HER2-positive advanced breast cancer by the US Food and Drug Administration (FDA) and the European Medicines Agency in 2013, while T-DXd was approved in the US in 2019 for HER2-positive metastatic or unresectable breast cancer [25][26][27]. Trastuzumab binds to HER2 domain IV, causing antibody-dependent cellular cytotoxicity (ADCC), antibodydependent cell phagocytosis (ADCP), HER2 internalization-mediated destruction, and dimerization inhibition [28][29][30].…”