@article{b31334250d3e42d9b589e880659e462c,
title = "Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance",
abstract = "Standard and targeted cancer therapies for late-stage cancer patients almost universally fail due to tumor heterogeneity/plasticity and intrinsic or acquired drug resistance. We used the telomerase substrate nucleoside precursor, 6-thio-2′-deoxyguanosine (6-thio-dG), to target telomerase-expressing non–small cell lung cancer cells resistant to EGFR-inhibitors and commonly used chemotherapy combinations. Colony formation assays, human xenografts as well as syngeneic and genetically engineered immune competent mouse models of lung cancer were used to test the effect of 6-thio-dG on targeted therapy– and chemotherapy-resistant lung cancer human cells and mouse models. We observed that erlotinib-, paclitaxel/carboplatin-, and gemcitabine/cisplatin-resistant cells were highly sensitive to 6-thio-dG in cell culture and in mouse models. 6-thio-dG, with a known mechanism of action, is a potential novel therapeutic approach to prolong disease control of therapy-resistant lung cancer patients with minimal toxicities.",
author = "Ilgen Mender and Ryan LaRanger and Krishna Luitel and Michael Peyton and Luc Girard and Lai, {Tsung Po} and Kimberly Batten and Crystal Cornelius and Dalvi, {Maithili P.} and Michael Ramirez and Wenting Du and Wu, {Lani F.} and Altschuler, {Steven J.} and Rolf Brekken and Martinez, {Elisabeth D.} and Minna, {John D.} and Wright, {Woodring E.} and Shay, {Jerry W.}",
note = "Funding Information: This work was supported by NCI SPORE P50CA70907 , the Johnson Foundation , and CPRIT . This work was performed in laboratories constructed with support from NIH grant C06 RR30414 . W. E. W. and J. W. S. hold the distinguished Southland Financial Corporation chair in Geriatrics Research. We also acknowledge the Cancer Intervention and Prevention Discovery Training Program Fellowship , RP160157 (I.M.), NSF PHY-1545915/SU2C (S.J.A.), and NCI-NIH RO1 CA185404 (L.F.W.). We thank Brenda Timmons, Jaewon Min, Enzo Tedone, and Melissa Coquelin for their technical help. Jerry W. Shay is a founding scientist for Barricade Therapeutics, LLC (Delaware, MD) and a SAB member of Reata Pharmaceuticals, Inc. (Irving, TX) and LifeLength (Madrid, Spain). Other authors declare no conflict of interest. Funding Information: This work was supported by NCI SPORE P50CA70907, the Johnson Foundation, and CPRIT. This work was performed in laboratories constructed with support from NIH grant C06 RR30414. W. E. W. and J. W. S. hold the distinguished Southland Financial Corporation chair in Geriatrics Research. We also acknowledge the Cancer Intervention and Prevention Discovery Training Program Fellowship, RP160157 (I.M.), NSF PHY-1545915/SU2C (S.J.A.), and NCI-NIH RO1 CA185404 (L.F.W.). We thank Brenda Timmons, Jaewon Min, Enzo Tedone, and Melissa Coquelin for their technical help. Jerry W. Shay is a founding scientist for Barricade Therapeutics, LLC (Delaware, MD) and a SAB member of Reata Pharmaceuticals, Inc. (Irving, TX) and LifeLength (Madrid, Spain). Other authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = aug,
doi = "10.1016/j.neo.2018.06.002",
language = "English (US)",
volume = "20",
pages = "826--837",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "8",
}