Everolimus exhibits efficacy as a radiosensitizer in a model of non-small cell lung cancer

Oncology Reports

Volumn 27, Issue 5, 2012, Pages 1625-1629

  Mauceri, Helena J ^a   Sutton, Harold G ^a   Darga, Thomas E ^a   Kocherginsky, Masha ^a   Kochanski, Joel ^b   Weichselbaum, Ralph R ^a   Vokes, Everett E ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b Maury Regional Medical Center   (United States)

Author keywords

Everolimus; Lung cancer; Radiation sensitization

Indexed keywords

ENDOTHELIN 1; EVEROLIMUS; GLUCOSE TRANSPORTER 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LACTATE DEHYDROGENASE; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; PROTEIN P21; VASCULOTROPIN A;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER INHIBITION; CANCER RADIOTHERAPY; CANCER RECURRENCE; CANCER SIZE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENTIATION; FEMALE; GENE EXPRESSION REGULATION; HUMAN; HUMAN CELL; IONIZING RADIATION; LUNG NON SMALL CELL CANCER; MONOTHERAPY; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; RADIATION DOSE FRACTIONATION; RADIATION RESPONSE; RADIOSENSITIZATION; TISSUE LEVEL;

ANIMALS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; COMBINED MODALITY THERAPY; FEMALE; GENE EXPRESSION; HUMANS; LUNG NEOPLASMS; MICE; MICE, NUDE; PHOSPHORYLATION; RADIATION, IONIZING; RADIATION-SENSITIZING AGENTS; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SIROLIMUS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84858189492     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or.2012.1666     Document Type: Article

References (26)

1. Meric-Bernstam F and Gonzalez-Angulo AM: Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 27: 2278-2287, 2009.
2. Klumpen HJ, Beijnen JH, Gurney H and Schellens JH: Inhibitors of mTOR. Oncologist 15: 1262-1269, 2010.
3. Vilar E, Perez-Garcia J and Tabernero J: Pushing the envelope in the mTOR pathway: the second generation of inhibitors. Mol Cancer Ther 10: 395-403, 2011
4. Huang S, Bjornsti MA and Houghton PJ: Rapamycins: mechanism of action and cellular resistance. Cancer Biol Ther 2: 222-232, 2003.
5. Fasolo A and Sessa C: Current and future directions in mammalian target of rapamycin inhibitors development. Expert Opin Investig Drugs 20: 381-394, 2011.
6. Wang X, Yue Kim YA, et al: Enhancing mammalian target of rapamycin (mTOR)-targeted cancer therapy by preventing mTOR/raptor inhibition-initiated, mTOR/rictor-independent Akt activation Cancer Res 68: 7409-7418, 2008.
7. Pal SK, Figlin RA and Reckamp K: Targeted therapies for non-small cell lung cancer: an evolving landscape. Mol Cancer Ther 9: 1931-1944, 2010.
8. Gridelli C, Maione P and Rossi A: The potential role of mTOR inhibitors in non-small cell lung cancer. Oncologist 13: 139-147, 2008. (Pubitemid 351342577)
9. Dhillon T, Mauri FA, Bellezza G, et al: Overexpression of the mammalian target of rapamycin: a novel biomarker for poor survival in resected early stage non-small cell lung cancer. J Thorac Oncol 5: 314-319, 2010.
10. Memmott RM and Dennis PA: The role of the Akt/mTOR pathway in tobacco carcinogen-induced lung tumorigenesis. Clin Cancer Res 16: 4-10, 2010.
11. Soria JC, Shepherd FA, Douillard JY, et al: Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors. Ann Oncol 20: 1674-1681, 2009.
12. Pu X, Hildebrandt MA, Lu C, et al: PI3K/PTEN/AKT/ mTOR pathway genetic variation predicts toxicity and distant progression in lung cancer patients receiving platinum-based chemotherapy Lung Cancer 71: 82-88, 2011.
13. Beuvink I, Boulay A, Fumagalli S, et al: The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation Cell 120: 747-759, 2005. (Pubitemid 40568794)
14. Wangpaichitr M, Wu C, You M, et al: Inhibition of mTOR restores cisplatin sensitivity through down-regulation of growth and anti-apoptotic proteins. Em i Pharmacol 591: 124-127, 2008.
15. Jaboin JJ, Shinohara ET, Moretti L, et al: The role of mTOR inhibition in augmenting radiation induced autophagy. Technol Cancer Res Treat 6: 443-447, 2007. (Pubitemid 47613293)
16. Shinohara ET, Cao C, Niermann K, et al: Enhanced radiation damage of tumor vasculature by mTOR inhibitors. Oncogene 24: 5414-5422, 2005. (Pubitemid 43080085)
17. Nagata Y, Takahashi A, Ohnishi K, et al: Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer cells having different p53 gene status. Int J Oncol 37: 1001-1010, 2010.
18. Kim KW, Moretti L, Mitchell LR, et al: Combined Bcl-2/ mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin Cancer Res 15: 6096-6105, 2009.
19. Manegold PC, Paringer C, Kulka U, et al: Antiangiogenic therapy with mammalian target of rapamycin inhibitor RAD001 (Everolimus) increases radiosensitivity in solid cancer. Clin Cancer Res 14: 892-900, 2008. (Pubitemid 351231174)
20. Hallahan DE, Mauceri HJ, Seung LP, et al: Spatial and temporal control of gene therapy using ionizing radiation. Nat Med 1: 786-791, 1995.
21. Janku F, Stewart DJ and Kurzrock R: Targeted therapy in non-small cell lung cancer - is it becoming a reality? Nat Rev Clin Oncol 7: 401-414, 2010.
22. O'Donnell A, Faivre S, Burris HA III, et al: Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol 26: 1588-1595, 2008.
23. Papadimitrakopoulou V, Soria JC, Douillard JY, Giaccone G, Wolf J, Crino L, Cappuzzo F, Sharma S, Gross SH and Shepherd FA: A phase II study of RAD001 (everolimus) mono-therapy in patients with advanced non-small cell lung cancer (NSCLC) failing prior platinum-based chemotherapy or prior C and EGFR inhibitors (EGFR-1). J Clin Oncol 25: 7589, 2007.
24. Milton DT, Kris MG, Azzoli CG, Gomez JE, Heelan R, Krug LM, Pao W, Pizzo B, Rizvi NA and Miller VA: PhaseI/II trial of gefitinib and RAD001 (Everolimus) in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 23: 7104, 2005.
25. Papadimitrakopoulou V, Blumenschein GR, Leighl NB, Bennouna J, Soria JC, Burns HA III, Dimitrijevic S, Kunz T, Di Scala L and Johnson BE: A phase 112 study investigating the combination of RAD001 (everolimus) and erlotinib as 2nd and 3rd line therapy in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy: phase 1 results. J Clin Oncol 26: 8051, 2008.
26. Majumder PK, Febbo PG, Bikoff R, et al: mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 10: 594-601, 2004.