Editors' ChoiceCancer

Targeted therapy with more punch

Sci. Signal.  01 Dec 2015:
Vol. 8, Issue 405, pp. ec358
DOI: 10.1126/scisignal.aad9391

Increased abundance of the human epidermal growth factor receptor 2 (HER2) is common in breast cancer, and high amounts of HER2 are associated with poor outcomes despite the availability of trastuzumab, an antibody against HER2, and other HER2-targeted agents. The reason for the poor outcomes is that many patients develop resistance to the targeted drugs. Müller et al. showed that this resistance can be overcome with trastuzumab emtansine, an antibody-drug conjugate that combines the HER2-targeting ability of trastuzumab with a cytotoxic drug, which the antibody delivers directly to the tumor. In addition to its cytotoxic effects, treatment with trastuzumab emtansine activated a strong antitumor immune response and effectively combined with immune checkpoint inhibitors, suggesting that this antibody-drug conjugate can be used in combination therapy.

P. Müller, M. Kreuzaler, T. Khan, D. S. Thommen, K. Martin, K. Glatz, S. Savic, N. Harbeck, U. Nitz, O. Gluz, M. von Bergwelt-Baildon, H. Kreipe, S. Reddy, M. Christgen, A. Zippelius, Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci. Transl. Med. 7, 315ra188 (2015). [Abstract]

M. Belvin, I. Mellman, Is all cancer therapy immunotherapy? Sci. Transl. Med. 7, 315fs48 (2015). [Abstract]