@article{00ae59cfada64082b07fa93a0ba97b65,
title = "Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer",
abstract = "Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs. SCLC TPCs possess a distinct transcriptional profile compared to non-TPCs, including elevated MYC activity. Genetic and pharmacological inhibition of MYC in SCLC cells to non-TPC levels inhibits long-term propagation but not short-term growth. These studies identify a highly tumorigenic population of SCLC cells in mouse models, cell lines, and patient tumors and a means to target them in this most fatal form of lung cancer.",
author = "Jahchan, {Nadine S.} and Lim, {Jing Shan} and Becky Bola and Karen Morris and Garrett Seitz and Tran, {Kim Q.} and Lei Xu and Francesca Trapani and Morrow, {Christopher J.} and Sandra Cristea and Coles, {Garry L.} and Dian Yang and Dedeepya Vaka and Kareta, {Michael S.} and Julie George and Mazur, {Pawel K.} and Thuyen Nguyen and Anderson, {Wade C.} and Dylla, {Scott J.} and Fiona Blackhall and Martin Peifer and Caroline Dive and Julien Sage",
note = "Funding Information: We thank Alejandro Sweet-Cordero, Monte Winslow, and Ann Cheung for helpful comments on the study; James Bradner for providing us with JQ1; Yanyan Zheng, David Simpson, Leanne Sayles, Shaheen Sikandar, Angera Kuo, Maider Zabala, Maddalena Adorno, Kipp Weiskopf, Jens-Peter Volkmer, and Geoffrey Krampitz for suggestions and help throughout the project; and Patty Lovelace and Jennifer Ho from the FACS facility and Natalia Kosovilka from the Protein and Nucleic Acid facility for technical support. Research reported in this publication was supported by a California TRDRP post-doctoral fellowship (N.S.J. and P.K.M.), the Stanford Cancer Institute (J.S.), the Stanford Cancer Biology T32 training grant (D.Y., J.S.L., and S.C.), the Stanford Tumor Biology T32 training grant (M.S.K.), the Stanford Child Health Research Institute (J.S. and M.S.K.), A ∗ STAR in Singapore (J.S.L.), the LUNGevity Foundation (J.S.), the German Ministry of Science and Education (BMBF) as part of the e:Med initiative (grants 01ZX1303A and 01ZX1406) (M.P.), Cancer Research UK core funding to CRUK Manchester Institute C5759/A20971 (C.D.), and the NIH (NCI R01CA201513) (J.S.). J.S. is the Harriet and Mary Zelencik Scientist in Children{\textquoteright}s Cancer and Blood Diseases. Publisher Copyright: {\textcopyright} 2016 The Author(s)",
year = "2016",
month = jul,
day = "19",
doi = "10.1016/j.celrep.2016.06.021",
language = "English (US)",
volume = "16",
pages = "644--656",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}