Naruto Taira
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Breast and Thyroid Surgery,
   Position   Professor
Article types 原著
Language English
Peer review Peer reviewed
Title YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development.
Journal Formal name：International journal of molecular sciences
Abbreviation：Int J Mol Sci
ISSN code：14220067/14220067
Domestic / ForeginForegin
Volume, Issue, Page 22(23)
Author and coauthor Fujihara Miwa, Shien Tadahiko, Shien Kazuhiko, Suzawa Ken, Takeda Tatsuaki, Zhu Yidan, Mamori Tomoka, Otani Yusuke, Yoshioka Ryo, Uno Maya, Suzuki Yoko, Abe Yuko, Hatono Minami, Tsukioki Takahiro, Takahashi Yuko, Kochi Mariko, Iwamoto Takayuki, Taira Naruto, Doihara Hiroyoshi, Toyooka Shinichi
Publication date 2021/11/26
Summary Trastuzumab-emtansine (T-DM1) is a therapeutic agent molecularly targeting human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and it is especially effective for MBC with resistance to trastuzumab. Although several reports have described T-DM1 resistance, few have examined the mechanism underlying T-DM1 resistance after the development of acquired resistance to trastuzumab. We previously reported that YES1, a member of the Src family, plays an important role in acquired resistance to trastuzumab in HER2-amplified breast cancer cells. We newly established a trastuzumab/T-DM1-dual-resistant cell line and analyzed the resistance mechanisms in this cell line. At first, the T-DM1 effectively inhibited the YES1-amplified trastuzumab-resistant cell line, but resistance to T-DM1 gradually developed. YES1 amplification was further enhanced after acquired resistance to T-DM1 became apparent, and the knockdown of the YES1 or the administration of the Src inhibitor dasatinib restored sensitivity to T-DM1. Our results indicate that YES1 is also strongly associated with T-DM1 resistance after the development of acquired resistance to trastuzumab, and the continuous inhibition of YES1 is important for overcoming resistance to T-DM1.
DOI 10.3390/ijms222312809
PMID 34884609