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Mechanisms underlying trastuzumab activity are complex

Nature Reviews Cardiology volume 12, page 669 (2015)Cite this article

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We would like to thank N. Mohan and W. J. Wu for their Correspondence (Trastuzumab is not a tyrosine kinase inhibitor. Nat. Rev. Cardiol. doi:10.1038/nrcardio.2015.135)1 on our Review (Cardiotoxicity of anticancer treatments. Nat. Rev. Cardiol. 12, 547–558; 2015),2 which raises some important issues. We acknowledge that our categorization of trastuzumab as a tyrosine kinase inhibitor (TKI) was scientifically inaccurate, and a Corrigendum has been published online and in print to rectify this error (Ewer, M. S. & Ewer, S. M. Cardiotoxicity of anticancer treatments. Nat. Rev. Cardiol. doi:10.1038/nrcardio.2015.133).3 The mechanisms underlying TKIs and monoclonal antibody cardiotoxicity are indeed complex, as pointed out in the Correspondence;1 these mechanistic facets go beyond the focus of our original paper. As noted, although pathways downstream of receptor tyrosine-protein kinase erbB-2 (ERBB2) can be downregulated by trastuzumab, growing evidence does not indicate that this effect is accomplished via inhibition of its kinase activity, a distinction that might carry important implications for our understanding of breast cancer biology and ERBB2-targeted therapy. A detailed discussion of these mechanistic considerations has been published previously.4 We are grateful for the opportunity to provide clarification regarding trastuzumab's mechanism of action.

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References

  1. Mohan, N. & Wu, W. J. Trastuzumab is not a tyrosine kinase inhibitor. Nat. Rev. Cardiol. http://dx.doi.org/10.1038/nrcardio.2015.135.

  2. Ewer, M. S. & Ewer, S. M. Cardiotoxicity of anticancer treatments. Nat. Rev. Cardiol. 12, 547–558 (2015).

    Article  CAS  Google Scholar 

  3. Ewer, M. S. & Ewer, S. M. Cardiotoxicity of anticancer treatments. Nat. Rev. Cardiol. http://dx.doi.org/10.1038/nrcardio.2015.133.

  4. Dokmanovic, M. & Wu, W. J. Trastuzumab-induced HER2 phosphorylation: exploring the mechanisms and implications. Receptors Clin. Investig. 1, e340 (2014).

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  1. Department of Cardiology, The University of Texas MD Anderson Cancer Centre, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Michael S. Ewer

  2. Division of Cardiovascular Medicine, School of Medicine & Public Health, University of Wisconsin, 600 Highland Avenue, Madison, 53792, WI, USA

    Steven M. Ewer

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  1. Michael S. Ewer
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  2. Steven M. Ewer
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Correspondence to Michael S. Ewer.

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Ewer, M., Ewer, S. Mechanisms underlying trastuzumab activity are complex. Nat Rev Cardiol 12, 669 (2015). https://doi.org/10.1038/nrcardio.2015.136

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