作者
Shun-Qing Liang, Elias D Bührer, Sabina Berezowska, Thomas M Marti, Duo Xu, Laurène Froment, Haitang Yang, Sean RR Hall, Erik Vassella, Zhang Yang, Gregor J Kocher, Michael A Amrein, Carsten Riether, Adrian F Ochsenbein, Ralph A Schmid, Ren-Wang Peng
发表日期
2019/1/31
期刊
Oncogene
卷号
38
期号
5
页码范围
622-636
出版商
Nature Publishing Group UK
简介
Oncogenic KRAS mutations comprise the largest subset of lung cancer defined by genetic alterations, but in the clinic no targeted therapies are available that effectively control mutational KRAS activation. Consequently, patients with KRAS-driven tumors are routinely treated with cytotoxic chemotherapy, which is often transiently effective owing to development of drug resistance. In this study, we show that hyperactivated mammalian target of rapamycin (mTOR) pathway is a characteristic hallmark of KRAS-mutant lung adenocarcinoma after chemotherapy treatment, and that KRAS-mutant lung cancer cells rely on persistent mTOR signaling to resist chemotherapeutic drugs. Coherently, mTOR inhibition circumvents the refractory phenotype and restores sensitivity of resistant KRAS-mutant lung cancer cells to chemotherapy. Importantly, drug combinations of clinically approved mTOR inhibitors and chemotherapy …
学术搜索中的文章
SQ Liang, ED Bührer, S Berezowska, TM Marti, D Xu… - Oncogene, 2019