@article{cd7d7bcbbac14b9cb9ea1c1722ebee7f,
title = "CHK1 inhibition in small-cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib",
abstract = "Effective targeted therapies for small-cell lung cancer (SCLC), cisplatin or the PARP inhibitor olaparib, and improved the the most aggressive form of lung cancer, remain urgently response of platinum-resistant models. Proteomic analysis needed. Here we report evidence of preclinical efficacy evoked identified CHK1 and MYC as top predictive biomarkers of by targeting the overexpressed cell-cycle checkpoint kinase LY2606368 sensitivity, suggesting that CHK1 inhibition may CHK1 in SCLC. Our studies employed RNAi-mediated atten-be especially effective in SCLC with MYC amplification or MYC uation or pharmacologic blockade with the novel second-protein overexpression. Our findings provide a preclinical generation CHK1 inhibitor prexasertib (LY2606368), currently proof of concept supporting the initiation of a clinical efficacy in clinical trials. In SCLC models in vitro and in vivo, LY2606368 trial in patients with platinum-sensitive or platinum-resistant exhibited strong single-agent efficacy, augmented the effects of relapsed SCLC.",
author = "Triparna Sen and Pan Tong and Stewart, {C. Allison} and Sandra Cristea and Aly Valliani and Shames, {David S.} and Redwood, {Abena B.} and Fan, {You Hong} and Lerong Li and Glisson, {Bonnie S.} and Minna, {John D.} and Julien Sage and Gibbons, {Don L.} and Helen Piwnica-Worms and Heymach, {John V.} and Jing Wang and Byers, {Lauren Averett}",
note = "Funding Information: The authors would like to thank Dr. Emily Roarty, Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center for reviewing and editing the manuscript. This work was supported by NIH (R01CA207295 to L.A. Byers), The University of Texas MD Anderson Cancer Center Small Cell Lung Cancer Working Group and Abell Hangar Foundation Distinguished Professor Endowment to B.S. Glisson, Sidney Kimmel Scholar Award to L.A. Byers, by Free to Breathe (formerly National Lung Cancer Research Partnership), North Carolina Lung Cancer Partnership (L.A. Byers), the LUNGevity Foundation (L.A. Byers), by Uniting Against Lung Cancer (L.A. Byers), R. Lee Clark Fellow Award, made possible by the Jeanne F. Shelby Scholarship Fund, to L.A. Byers, MD Anderson Physician Scientist Award to L.A. Byers, National Cancer Institute Cancer Clinical Investigator Team Leadership Award (P30 CA016672 to L.A. Byers), the generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program, and The Susan G. Komen Foundation award to H. Piwnica-Worms. LY2606368 and olaparib provided by The Pharmaceutical Chemistry Facility at MD Anderson, supported by the NIH/National Cancer Institute (P30CA016672); flow cytometry studies done at The Flow Cytometry and Cellular Imaging Core Facility, North Campus, The University of Texas MD Anderson Cancer Center, funded by NCI Cancer Center Support Grant (P30CA016672). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher Copyright: {\textcopyright}2017 AACR.",
year = "2017",
month = jul,
day = "15",
doi = "10.1158/0008-5472.CAN-16-3409",
language = "English (US)",
volume = "77",
pages = "3870--3884",
journal = "Cancer Research",
issn = "0008-5472",
number = "14",
}