| Literature DB >> 27070703 |
Wei Wei1, Young Shik Shin2, Min Xue3, Tomoo Matsutani4, Kenta Masui4, Huijun Yang4, Shiro Ikegami4, Yuchao Gu4, Ken Herrmann5, Dazy Johnson5, Xiangming Ding6, Kiwook Hwang3, Jungwoo Kim3, Jian Zhou6, Yapeng Su3, Xinmin Li6, Bruno Bonetti7, Rajesh Chopra8, C David James9, Webster K Cavenee4, Timothy F Cloughesy10, Paul S Mischel11, James R Heath12, Beatrice Gini4.
Abstract
Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistance, including in the highly lethal brain cancer glioblastoma (GBM). We performed single-cell phosphoproteomics on a patient-derived in vivo GBM model of mTOR kinase inhibitor resistance and coupled it to an analytical approach for detecting changes in signaling coordination. Alterations in the protein signaling coordination were resolved as early as 2.5 days after treatment, anticipating drug resistance long before it was clinically manifest. Combination therapies were identified that resulted in complete and sustained tumor suppression in vivo. This approach may identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations.Entities:
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Year: 2016 PMID： 27070703 PMCID： PMC4831071 DOI： 10.1016/j.ccell.2016.03.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743