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  3. MEK and PI3K catalytic activity as predictor of the response to molecularly targeted agents in triple-negative breast cancer

MEK and PI3K catalytic activity as predictor of the response to molecularly targeted agents in triple-negative breast cancer

  • Biochem Biophys Res Commun. 2017 Aug 5;489(4):484-489. doi: 10.1016/j.bbrc.2017.05.177.
Natsuki Sato 1,  Masayuki Wakabayashi 2,  Masatoshi Nakatsuji 3,  Haruka Kashiwagura 2,  Naohiro Shimoji 3,  Shiho Sakamoto 3,  Atsuko Ishida 3,  Jangsoon Lee 4,  Bora Lim 4,  Naoto T Ueno 4,  Hideki Ishihara 5,  Takashi Inui 6
Affiliations

Affiliations

  • 1 R&D Department, Nittobo Medical Co., Ltd., 1, Shiojima, Fukuhara, Fukuyama, Koriyama, Fukushima 963-8091, Japan; Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
  • 2 R&D Department, Nittobo Medical Co., Ltd., 1, Shiojima, Fukuhara, Fukuyama, Koriyama, Fukushima 963-8091, Japan.
  • 3 Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
  • 4 Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
  • 5 R&D Department, Nittobo Medical Co., Ltd., 1, Shiojima, Fukuhara, Fukuyama, Koriyama, Fukushima 963-8091, Japan. Electronic address: ishiharah@nittobogrp.com.
  • 6 Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: inuit@bioinfo.osakafu-u.ac.jp.
PMID: 28576487 DOI: 10.1016/j.bbrc.2017.05.177
Abstract

Hyper-activation of the MAPK and PI3K-AKT pathways is linked to tumour progression in triple-negative breast Cancer (TNBC). However, clinically effective predictive markers for drugs targeted against protein kinases involved in these pathways have not been identified. We investigated the ability of MEK and PI3K catalytic activity to predict sensitivity to trametinib and wortmannin in TNBC. MEK and PI3K activities correlated strongly with each Other only in cell lines showing wortmannin-specific sensitivity, as shown by a linear regression curve (R = 0.951). Accordingly, we created a new parameter that distinguishes trametinib and wortmannin sensitivity in vitro and in vivo. Our findings suggest that the catalytic activities of MEK and PI3K might predict the response of TNBC to trametinib and wortmannin.

Keywords

Catalytic activity; Drug sensitivity; MEK; PI3K; Triple-negative breast cancer.

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