Mechanisms contributing to ado-trastuzumab emtansine-induced toxicities: a gateway to better understanding of ADC-associated toxicities

19Citations
Citations of this article
16Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

In order to improve the safety of novel therapeutic drugs, better understanding of the mechanisms of action is important. Ado-trastuzumab emtansine (also known as T-DM1) is an antibody-drug conjugate (ADC) approved for the treatment of HER2-positive breast cancer. While the treatment with T-DM1 results in significant efficacy in the selected patient population, nonetheless, there are concerns with side effects such as thrombocytopenia and hepatotoxicity. While current understanding of the mechanism of T-DM1-mediated side effects is still incomplete, there have been several reports of HER2-dependent and/or -independent mechanisms that could be associated with the T-DM1-induced adverse events. This review highlights the importance of HER2-independent mechanism of T-DM1 to induce hepatotoxicity, which offers a new insight into a role for CKAP5 in the overall maytansinoid-based ADC (DM1 and DM4)-mediated cytotoxicity. This discovery provides a molecular basis for T-DM1-induced off-target toxicity and opens a new avenue for developing the next generation of ADCs.

Cite

CITATION STYLE

APA

Endo, Y., Mohan, N., Dokmanovic, M., & Wu, W. J. (2021, January 1). Mechanisms contributing to ado-trastuzumab emtansine-induced toxicities: a gateway to better understanding of ADC-associated toxicities. Antibody Therapeutics. Oxford University Press. https://doi.org/10.1093/abt/tbab005

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free