Therapeutic Effects of Repurposed Therapies in Non-Small Cell Lung Cancer: What Is Old Is New Again

Overview

Journal Oncologist

Publisher Oxford University Press

Specialty Oncology

Date 2015 Jul 10

PMID 26156329

Citations 16

Authors

Ashish Saxena

Daniel Becker

Isabel Preeshagul

Karen Lee

Elena Katz

Benjamin Levy

Affiliations

Soon will be listed here.

Abstract

The recent emergence of targeted and immunotherapeutic agents has dramatically changed the management for patients with non-small cell lung cancer (NSCLC). Despite these advances, lung cancer is not exempt from the challenges facing oncology drug development, including the huge financial cost and the time required for drug implementation. Repositioning noncancer therapies with potential antineoplastic properties into new therapeutic niches is an alternative treatment strategy offering the possibility of saving money and time and improving outcomes. The goal of such a strategy is to deliver an effective drug with a favorable toxicity profile at a reduced cost. Preclinical models and observational data have demonstrated promising activity for many of these agents, and they are now being studied in prospective trials. We review the relevant published data regarding the therapeutic effects of metformin, statins, nonsteroidal anti-inflammatory drugs, β-blockers, and itraconazole in NSCLC, with a focus on the putative mechanisms of action and clinical data. As these drugs are increasingly being tested in clinical trials, we aim to highlight the salient challenges and future strategies to optimize this approach.

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References

Rothwell P, Wilson M, Elwin C, Norrving B, Algra A, Warlow C . Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010; 376(9754):1741-50. DOI: 10.1016/S0140-6736(10)61543-7. View

Sanli T, Liu C, Rashid A, Hopmans S, Tsiani E, Schultz C . Lovastatin sensitizes lung cancer cells to ionizing radiation: modulation of molecular pathways of radioresistance and tumor suppression. J Thorac Oncol. 2011; 6(3):439-50. DOI: 10.1097/JTO.0b013e3182049d8b. View

Han J, Lee S, Yoo N, Hyung L, Moon Y, Yun T . A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2011; 17(6):1553-60. DOI: 10.1158/1078-0432.CCR-10-2525. View

Koch A, Bergman B, Holmberg E, Sederholm C, Ek L, Kosieradzki J . Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: a double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group. Eur J Cancer. 2011; 47(10):1546-55. DOI: 10.1016/j.ejca.2011.03.035. View

Li X, Zhang N, Li Y, Shi Y, Li D, Xie Y . Effects of metformin and rosiglitazone on peripheral insulin resistance and β-cell function in obesity: a double-blind, randomized, controlled study. J Int Med Res. 2011; 39(2):358-65. DOI: 10.1177/147323001103900203. View

Hwang K, Na K, Park D, Choi K, Kim B, Shim H . Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of survivin. Invest New Drugs. 2010; 29(5):945-52. DOI: 10.1007/s10637-010-9450-2. View

Aftab B, Dobromilskaya I, Liu J, Rudin C . Itraconazole inhibits angiogenesis and tumor growth in non-small cell lung cancer. Cancer Res. 2011; 71(21):6764-72. PMC: 3206167. DOI: 10.1158/0008-5472.CAN-11-0691. View

Tan B, Yao W, Ge J, Peng X, Du X, Zhang R . Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes. Cancer. 2011; 117(22):5103-11. DOI: 10.1002/cncr.26151. View

Wang H, Liao Z, Komaki R, Welsh J, OReilly M, Chang J . Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Ann Oncol. 2013; 24(5):1312-9. PMC: 3629895. DOI: 10.1093/annonc/mds616. View

10.

Storozhuk Y, Hopmans S, Sanli T, Barron C, Tsiani E, Cutz J . Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer. 2013; 108(10):2021-32. PMC: 3670487. DOI: 10.1038/bjc.2013.187. View

11.

Morgillo F, Sasso F, Della Corte C, Vitagliano D, DAiuto E, Troiani T . Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines. Clin Cancer Res. 2013; 19(13):3508-19. DOI: 10.1158/1078-0432.CCR-12-2777. View

12.

Lin C, Yeh H, Huang W, Yan J, Lai W, Su W . Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway. Am J Respir Cell Mol Biol. 2013; 49(2):241-50. DOI: 10.1165/rcmb.2012-0244OC. View

13.

Quinn B, Kitagawa H, Memmott R, Gills J, Dennis P . Repositioning metformin for cancer prevention and treatment. Trends Endocrinol Metab. 2013; 24(9):469-80. DOI: 10.1016/j.tem.2013.05.004. View

14.

Li L, Han R, Xiao H, Lin C, Wang Y, Liu H . Metformin sensitizes EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal. Clin Cancer Res. 2014; 20(10):2714-26. DOI: 10.1158/1078-0432.CCR-13-2613. View

15.

Shim J, Liu J . Recent advances in drug repositioning for the discovery of new anticancer drugs. Int J Biol Sci. 2014; 10(7):654-63. PMC: 4081601. DOI: 10.7150/ijbs.9224. View

16.

Pisanti S, Picardi P, Ciaglia E, Dalessandro A, Bifulco M . Novel prospects of statins as therapeutic agents in cancer. Pharmacol Res. 2014; 88:84-98. DOI: 10.1016/j.phrs.2014.06.013. View

17.

Fasano M, Della Corte C, Capuano A, Sasso F, Papaccio F, Berrino L . A multicenter, open-label phase II study of metformin with erlotinib in second-line therapy of stage IV non-small-cell lung cancer patients: treatment rationale and protocol dynamics of the METAL trial. Clin Lung Cancer. 2014; 16(1):57-9. DOI: 10.1016/j.cllc.2014.06.010. View

18.

Bockorny B, Dasanu C . HMG-CoA reductase inhibitors as adjuvant treatment for hematologic malignancies: what is the current evidence?. Ann Hematol. 2014; 94(1):1-12. PMC: 7079888. DOI: 10.1007/s00277-014-2236-4. View

19.

Edelman M, Tan M, Fidler M, Sanborn R, Otterson G, Sequist L . Randomized, double-blind, placebo-controlled, multicenter phase II study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer. J Clin Oncol. 2014; 33(2):189-94. PMC: 4890680. DOI: 10.1200/JCO.2014.55.5789. View

20.

Lin J, Gallagher E, Sigel K, Mhango G, Galsky M, Smith C . Survival of patients with stage IV lung cancer with diabetes treated with metformin. Am J Respir Crit Care Med. 2014; 191(4):448-54. PMC: 4351595. DOI: 10.1164/rccm.201407-1395OC. View