Clinical efficacy of mTOR inhibitors in solid tumors: A systematic review

Future Oncology

Volumn 11, Issue 11, 2015, Pages 1687-1699

  Huang, Zebo ^a   Wu, Yinxia ^b   Zhou, Xin ^a   Qian, Jiaqi ^a   Zhu, Wei ^a   Shu, Yongqian ^a   Liu, Ping ^a  

^a THE FIRST AFFILIATED HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

^b CLINICAL MEDICAL COLLEGE OF YANGZHOU UNIVERSITY   (China)

Author keywords

clinical trials; mTOR inhibitor; solid tumor

Indexed keywords

EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; RAPAMYCIN; RIDAFOROLIMUS; TEMSIROLIMUS; ANTI-IGF-1R ANTIBODY A12; ANTINEOPLASTIC AGENT; BEVACIZUMAB; DOCETAXEL; ERLOTINIB; GEFITINIB; IMATINIB; MONOCLONAL ANTIBODY; PROTEIN KINASE INHIBITOR; QUINAZOLINE DERIVATIVE; TARGET OF RAPAMYCIN KINASE; TAXOID;

ANTINEOPLASTIC ACTIVITY; BLOOD TOXICITY; CANCER CHEMOTHERAPY; DRUG EFFICACY; FATIGUE; FOOD AND DRUG ADMINISTRATION; HUMAN; MONOTHERAPY; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REVIEW; SOLID TUMOR; STOMATITIS; SYSTEMATIC REVIEW; THERAPY EFFECT; TREATMENT OUTCOME; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; NEOPLASMS; PATHOLOGY; SIGNAL TRANSDUCTION;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BEVACIZUMAB; CLINICAL TRIALS AS TOPIC; ERLOTINIB HYDROCHLORIDE; EVEROLIMUS; HUMANS; IMATINIB MESYLATE; NEOPLASMS; PROTEIN KINASE INHIBITORS; QUINAZOLINES; SIGNAL TRANSDUCTION; SIROLIMUS; TAXOIDS; TOR SERINE-THREONINE KINASES;

EID: 84930579368     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.15.70     Document Type: Review

References (81)

1. Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J. Clin. Oncol. 28(6), 1075-1083 (2010).
2. Sabatini DM. mTOR and cancer: insights into a complex relationship. Nat. Rev. Cancer 6(9), 729-734 (2006).
3. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 12(1), 9-22 (2007).
4. Vignot S, Faivre S, Aguirre D, Raymond E. mTOR-targeted therapy of cancer with rapamycin derivatives. Ann. Oncol. 16(4), 525-537 (2005).
5. Yuan R, Kay A, Berg WJ, Lebwohl D. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J. Hematol. Oncol. 2, 45 (2009).
6. Torisel (temsirolimus) package insert. Philadelphia Wyeth Pharmaceuticals, PA, USA (2008).
7. Afinitor (everolimus) package insert. Novartis Pharmaceuticals. East Hanover, NJ, USA (2009).
8. Hudes G, Carducci M, Tomczak P et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 356(22), 2271-2281 (2007).
9. Motzer RJ, Escudier B, Oudard S et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer 116(18), 4256-4265 (2010).
10. Yao JC, Shah MH, Ito T et al. Everolimus for advanced pancreatic neuroendocrine tumors. N. Engl. J. Med. 364(6), 514-523 (2011).
11. Baselga J, Campone M, Piccart M et al. Everolimus in postmenopausal hormonereceptor-positive advanced breast cancer. N. Engl. J. Med. 366(6), 520-529 (2012).
12. Krueger DA, Care MM, Holland K et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N. Engl. J. Med. 363(19), 1801-1811 (2010).
13. ClinicalTrials.gov. www.clinicaltrials.gov
14. Ohtsu A, Ajani JA, Bai YX et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, Phase III GRANITE-1 study. J. Clin. Oncol. 31(31), 3935-3943 (2013).
15. Ng K, Tabernero J, Hwang J et al. Phase II study of everolimus in patients with metastatic colorectal adenocarcinoma previously treated with bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Clin. Cancer Res. 19(14), 3987-3995 (2013).
16. Demetri GD, Chawla SP, Ray-Coquard I et al. Results of an international randomized Phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J. Clin. Oncol. 31(19), 2485-2492 (2013).
17. Chawla SP, Staddon AP, Baker LH et al. Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas. J. Clin. Oncol. 30(1), 78-84 (2012).
18. Yoo C, Lee J, Rha SY et al. Multicenter Phase II study of everolimus in patients with metastatic or recurrent bone and soft-tissue sarcomas after failure of anthracycline and ifosfamide. Invest. New Drugs 31(6), 1602-1608 (2013).
19. Schwartz GK, Tap WD, Qin LX et al. Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, Phase 2 trial. Lancet Oncol. 14(4), 371-382 (2013).
20. Rizell M, Andersson M, Cahlin C et al. Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer. Int J. Clin. Oncol. 13(1), 66-70 (2008).
21. Tinker AV, Ellard S, Welch S et al. Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199). Gynecol Oncol. 130(2), 269-274 (2013).
22. Stacchiotti S, Marrari A, Tamborini E et al. Response to imatinib plus sirolimus in advanced chordoma. Ann. Oncol. 20(11), 1886-1894 (2009).
23. Altomare I, Bendell JC, Bullock KE et al. A Phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer. Oncologist 16(8), 1131-1137 (2011).
24. Slomovitz BM, Lu KH, Johnston T et al. A Phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer 116(23), 5415-5419 (2010).
25. Oza AM, Elit L, Tsao MS et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J. Clin. Oncol. 29(24), 3278-3285 (2011).
26. Colombo N, McMeekin DS, Schwartz PE et al. Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, Phase 2 trial. Br. J. Cancer 108(5), 1021-1026 (2013).
27. Doi T, Muro K, Boku N et al. Multicenter Phase II study of everolimus in patients with previously treated metastatic gastric cancer. J. Clin. Oncol. 28(11), 1904-1910 (2010).
28. Chang SM, Wen P, Cloughesy T et al. Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme. Invest. New Drugs 23(4), 357-361 (2005).
29. Galanis E, Buckner JC, Maurer MJ et al. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J. Clin. Oncol. 23(23), 5294-5304 (2005).
30. Lassen U, Sorensen M, Gaziel TB et al. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res. 33(4), 1657-1660 (2013).
31. Decaens T, Luciani A, Itti E et al. Phase II study of sirolimus in treatmentnaive patients with advanced hepatocellular carcinoma. Dig. Liver Dis. 44(7), 610-616 (2012).
32. Bauman JE, Arias-Pulido H, Lee SJ et al. A Phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. Oral Oncol. 49(5), 461-467 (2013).
33. Hainsworth JD, Infante JR, Spigel DR et al. Bevacizumab and everolimus in the treatment of patients with metastatic melanoma: a Phase 2 trial of the Sarah Cannon Oncology Research Consortium. Cancer 116(17), 4122-4129 (2010).
34. Duran I, Kortmansky J, Singh D et al. A Phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br. J. Cancer 95(9), 1148-1154 (2006).
35. Reungwetwattana T, Molina JR, Mandrekar SJ et al. Brief report: a Phase II ?window-ofopportunity? frontline study of the MTOR inhibitor, temsirolimus given as a single agent in patients with advanced NSCLC, an NCCTG study. J. Thorac. Oncol. 7(5), 919-922 (2012).
36. Price KA, Azzoli CG, Krug LM et al. Phase II trial of gefitinib and everolimus in advanced non-small cell lung cancer. J. Thorac. Oncol. 5(10), 1623-1629 (2010).
37. Ramalingam SS, Owonikoko TK, Behera M et al. Phase II study of docetaxel in combination with everolimus for second- or third-line therapy of advanced non-small-cell lung cancer. J. Thorac. Oncol. 8(3), 369-372 (2013).
38. Wolpin BM, Hezel AF, Abrams T et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J. Clin. Oncol. 27(2), 193-198 (2009).
39. Kruczek K, Ratterman M, Tolzien K et al. A Phase II study evaluating the toxicity and efficacy of single-agent temsirolimus in chemotherapy-naive castration-resistant prostate cancer. Br. J. Cancer 109(7), 1711-1716 (2013).
40. Armstrong AJ, Shen T, Halabi S et al. A Phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer. Clin. Genitourin. Cancer 11(4), 397-406 (2013).
41. Schuetze SM, Zhao L, Chugh R et al. Results of a Phase II study of sirolimus and cyclophosphamide in patients with advanced sarcoma. Eur. J. Cancer 48(9), 1347-1353 (2012).
42. Tarhini A, Kotsakis A, Gooding W et al. Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. Clin. Cancer Res. 16(23), 5900-5907 (2010).
43. Okuno S, Bailey H, Mahoney MR et al. A Phase 2 study of temsirolimus (CCI-779) in patients with soft tissue sarcomas: a study of the Mayo Phase 2 consortium (P2C). Cancer 117(15), 3468-3475 (2011).
44. Seront E, Rottey S, Sautois B et al. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Ann. Oncol. 23(10), 2663-2670 (2012).
45. Milowsky MI, Iyer G, Regazzi AM et al. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 112(4), 462-470 (2013).
46. Liu P, Cheng H, Roberts TM et al. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat. Rev. Drug Discov. 8(8), 627-644 (2009).
47. Dancey J. mTOR signaling and drug development in cancer. Nat. Rev. Clin. Oncol. 7(4), 209-219 (2010).
48. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441(7092), 424-430 (2006).
49. Easton JB, Houghton PJ. mTOR and cancer therapy. Oncogene 25(48), 6436-6446 (2006).
50. Li SY, Rong M, Grieu F, Iacopetta B. PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res. Treat. 96(1), 91-95 (2006).
51. Shayesteh L, Lu Y, Kuo WL et al. PIK3CA is implicated as an oncogene in ovarian cancer. Nat. Genet. 21(1), 99-102 (1999).
52. Oda K, Stokoe D, Taketani Y et al. High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res. 65(23), 10669-10673 (2005).
53. Risinger JI, Hayes AK, Berchuck A et al. PTEN/MMAC1 mutations in endometrial cancers. Cancer Res. 57(21), 4736-4738 (1997).
54. Li J, Yen C, Liaw D et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275(5308), 1943-1947 (1997).
55. Steck PA, Pershouse MA, Jasser SA et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15(4), 356-362 (1997).
56. Lam JS, Shvarts O, Leppert JT et al. Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy. J. Urol. 173(6), 1853-1862 (2005).
57. Inoki K, Ouyang H, Li Y et al. Signaling by target of rapamycin proteins in cell growth control. Microbiol. Mol. Biol. Rev. 69(1), 79-100 (2005).
58. Giardiello FM, Welsh SB, Hamilton SR et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N. Engl. J. Med. 316(24), 1511-1514 (1987).
59. Sorrells DL, Meschonat C, Black D et al. Pattern of amplification and overexpression of the eukaryotic initiation factor 4E gene in solid tumor. J. Surg. Res. 85(1), 37-42 (1999).
60. Sorrells DJ, Ghali GE, De Benedetti A et al. Progressive amplification and overexpression of the eukaryotic initiation factor 4E gene in different zones of head and neck cancers. J. Oral Maxillofac. Surg. 57(3), 294-299 (1999).
61. Wang S, Lloyd RV, Hutzler MJ et al. Expression of eukaryotic translation initiation factors 4E and 2alpha correlates with the progression of thyroid carcinoma. Thyroid 11(12), 1101-1107 (2001).
62. Rosenwald IB, Chen JJ, Wang S et al. Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis. Oncogene 18(15), 2507-2517 (1999).
63. Li BD, Liu L, Dawson M et al. Overexpression of eukaryotic initiation factor 4E (eIF4E) in breast carcinoma. Cancer 79(12), 2385-2390 (1997).
64. Crew JP, Fuggle S, Bicknell R et al. Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression. Br. J. Cancer 82(1), 161-166 (2000).
65. Couch FJ, Wang XY, Wu GJ et al. Localization of PS6K to chromosomal region 17q23 and determination of its amplification in breast cancer. Cancer Res. 59(7), 1408-1411 (1999).
66. Liu Q, Thoreen C, Wang J et al. mTOR mediated anti-cancer drug discovery. Drug Discov. Today Ther. Strateg. 6(2), 47-55 (2009).
67. Garcia-Echeverria C. Blocking the mTOR pathway: a drug discovery perspective. Biochem. Soc. Trans. 39(2), 451-455 (2011).
68. Guertin DA, Sabatini DM. The pharmacology of mTOR inhibition. Sci. Signal. 2(67), e24 (2009).
69. Efeyan A, Sabatini DM. mTOR and cancer: many loops in one pathway. Curr. Opin. Cell Biol. 22(2), 169-176 (2010).
70. Mao JH, Kim IJ, Wu D et al. FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science 321(5895), 1499-1502 (2008).
71. Wagle N, Grabiner BC, Van Allen EM et al. Activating mTOR mutations in a patient with an extraordinary response on a Phase I trial of everolimus and pazopanib. Cancer Discov. 4(5), 546-553 (2014).
72. Chresta CM, Davies BR, Hickson I et al. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 70(1), 288-298 (2010).
73. Bhagwat SV, Gokhale PC, Crew AP et al. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Mol. Cancer Ther. 10(8), 1394-1406 (2011).
74. Janne PA, Cohen RB, Laird AD et al. Phase I safety and pharmacokinetic study of the PI3K/mTOR inhibitor SAR245409 (XL765) in combination with erlotinib in patients with advanced solid tumors. J. Thorac. Oncol. 9(3), 316-323 (2014).
75. Venkatesan AM, Dehnhardt CM, Delos SE et al. Bis (morpholino-1,3,5-triazine) derivatives: potent adenosine 5?-triphosphate competitive phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor. J. Med. Chem. 53(6), 2636-2645 (2010).
76. Maira SM, Stauffer F, Brueggen J et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol. Cancer Ther. 7(7), 1851-1863 (2008).
77. Baumann P, Schneider L, Mandl-Weber S et al. Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in multiple myeloma. Anticancer Drugs 23(1), 131-138 (2012).
78. Garlich JR, De P, Dey N et al. A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. Cancer Res. 68(1), 206-215 (2008).
79. Yuan J, Mehta PP, Yin MJ et al. PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity. Mol. Cancer Ther. 10(11), 2189-2199 (2011).
80. Sutherlin DP, Bao L, Berry M et al. Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer. J. Med. Chem. 54(21), 7579-7587 (2011).
81. Knight SD, Adams ND, Burgess JL et al. Discovery of GSK2126458, a highly potent inhibitor of PI3K and the mammalian target of rapamycin. ACS Med. Chem. Lett. 1(1), 39-43 (2010).