Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618302525 |
| _version_ | 1818197972313178112 |
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| author | Ilgen Mender Ryan LaRanger Krishna Luitel Michael Peyton Luc Girard Tsung-Po Lai Kimberly Batten Crystal Cornelius Maithili P. Dalvi Michael Ramirez Wenting Du Lani F. Wu Steven J. Altschuler Rolf Brekken Elisabeth D. Martinez John D. Minna Woodring E. Wright Jerry W. Shay |
| author_facet | Ilgen Mender Ryan LaRanger Krishna Luitel Michael Peyton Luc Girard Tsung-Po Lai Kimberly Batten Crystal Cornelius Maithili P. Dalvi Michael Ramirez Wenting Du Lani F. Wu Steven J. Altschuler Rolf Brekken Elisabeth D. Martinez John D. Minna Woodring E. Wright Jerry W. Shay |
| author_sort | Ilgen Mender |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T01:58:28Z |
| format | Article |
| id | doaj.art-4cb2a9b75e64451da5d6b5d27e43a411 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-12T01:58:28Z |
| publishDate | 2018-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-4cb2a9b75e64451da5d6b5d27e43a4112022-12-22T00:42:16ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862018-08-01208826837Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy ResistanceIlgen Mender0Ryan LaRanger1Krishna Luitel2Michael Peyton3Luc Girard4Tsung-Po Lai5Kimberly Batten6Crystal Cornelius7Maithili P. Dalvi8Michael Ramirez9Wenting Du10Lani F. Wu11Steven J. Altschuler12Rolf Brekken13Elisabeth D. Martinez14John D. Minna15Woodring E. Wright16Jerry W. Shay17Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAGreen Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USADepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USADepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USADepartment of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Division of Surgical Oncology, Department of Surgery and Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TXHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USAHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Division of Surgical Oncology, Department of Surgery and Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TXDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Address all correspondence to: Jerry W. Shay, UT Southwestern Medical Center, Department of Cell Biology, 6000 Harry Hines Boulevard, Dallas, Texas 75390.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.http://www.sciencedirect.com/science/article/pii/S1476558618302525 |
| spellingShingle | Ilgen Mender Ryan LaRanger Krishna Luitel Michael Peyton Luc Girard Tsung-Po Lai Kimberly Batten Crystal Cornelius Maithili P. Dalvi Michael Ramirez Wenting Du Lani F. Wu Steven J. Altschuler Rolf Brekken Elisabeth D. Martinez John D. Minna Woodring E. Wright Jerry W. Shay Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance Neoplasia: An International Journal for Oncology Research |
| title | Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance |
| title_full | Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance |
| title_fullStr | Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance |
| title_full_unstemmed | Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance |
| title_short | Telomerase-Mediated Strategy for Overcoming Non–Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance |
| title_sort | telomerase mediated strategy for overcoming non small cell lung cancer targeted therapy and chemotherapy resistance |
| url | http://www.sciencedirect.com/science/article/pii/S1476558618302525 |
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