VS-5584, a novel PI3K-mTOR dual inhibitor, inhibits melanoma cell growth in vitro and in vivo

PLoS ONE

Volumn 10, Issue 7, 2015, Pages

  Shao, Zheren ^a   Bao, Qi ^a   Jiang, Fangzhen ^a   Qian, Huan ^a   Fang, Quan ^a   Hu, Xueqing ^a  

^a ZHEJIANG UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; 5 (9 ISOPROPYL 8 METHYL 2 MORPHOLINO 9H PURIN 6 YL) 2 PYRIMIDINAMINE; CASPASE 3; CASPASE 9; CYCLIN D1; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN KINASE B; SMALL INTERFERING RNA; ANTINEOPLASTIC AGENT; MORPHOLINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PURINE DERIVATIVE; TARGET OF RAPAMYCIN KINASE; VS-5584;

A 2058 CELL LINE; A375 CELL LINE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CANCER SURVIVAL; CELL SURVIVAL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG POTENTIATION; ENZYME ACTIVATION; ENZYME INHIBITION; GENE SILENCING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; KERATINOCYTE; MALE; MELANOCYTE; MELANOMA; MELANOMA CELL LINE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; RNA INTERFERENCE; SK MEL 3 CELL LINE; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; DRUG EFFECTS; DRUG SCREENING; ENZYMOLOGY; GENE EXPRESSION REGULATION; SKIN NEOPLASMS; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MALE; MELANOMA; MICE; MORPHOLINES; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN KINASE INHIBITORS; PURINES; SKIN NEOPLASMS; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84941780580     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0132655     Document Type: Article

References (26)

1. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64: 9-29. doi: 10. 3322/caac.21208 PMID: 24399786
2. Hutchinson L (2015) Skin cancer. Golden age of melanoma therapy. Nat Rev Clin Oncol 12: 1. doi: 10. 1038/nrclinonc.2014.219 PMID: 25511188
3. Webster RM, Mentzer SE (2014) The malignant melanoma landscape. Nat Rev Drug Discov 13: 491-492. doi: 10.1038/nrd4326 PMID: 24981356
4. Schadendorf D, Hauschild A (2014) Melanoma in 2013: Melanoma - the run of success continues. Nat Rev Clin Oncol 11: 75-76. doi: 10.1038/nrclinonc.2013.246 PMID: 24419300
5. Hutchinson L (2014) Skin cancer: less is as good as more in refractory melanoma. Nat Rev Clin Oncol 11: 502.
6. Tang KD, Ling MT (2014) Targeting drug-resistant prostate cancer with dual PI3K/mTOR inhibition. Curr Med Chem 21: 3048-3056. PMID: 24735368
7. Fruman DA, Rommel C (2014) PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 13: 140-156. doi: 10.1038/nrd4204 PMID: 24481312
8. Vanhaesebroeck B, Stephens L, Hawkins P (2012) PI3K signalling: the path to discovery and understanding. Nat Rev Mol Cell Biol 13: 195-203. doi: 10.1038/nrm3290 PMID: 22358332
9. Davies MA (2012) The role of the PI3K-AKT pathway in melanoma. Cancer J 18: 142-147. doi: 10. 1097/PPO.0b013e31824d448c PMID: 22453015
10. Meier F, Schittek B, Busch S, Garbe C, Smalley K, Satyamoorthy K, et al. (2005) The RAS/RAF/MEK/ ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma. Front Biosci 10: 2986-3001. PMID: 15970553
11. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4: 988-1004. PMID: 16341064
12. Edlind MP, Hsieh AC (2014) PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance. Asian J Androl 16: 378-386. doi: 10.4103/1008-682X.122876 PMID: 24759575
13. Hart S, Novotny-Diermayr V, Goh KC, Williams M, Tan YC, Ong LC, et al. (2013) VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther 12: 151-161. doi: 10.1158/1535-7163.MCT-12-0466 PMID: 23270925
14. Risberg K, Fodstad O, Andersson Y (2011) Synergistic anticancer effects of the 9.2.27PE immunotoxin and ABT-737 in melanoma. PLoS One 6: e24012. doi: 10.1371/journal.pone.0024012 PMID: 21915275
15. Hikita H, Takehara T, Shimizu S, Kodama T, Shigekawa M, Iwase K, et al. (2010) The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib. Hepatology 52: 1310-1321. doi: 10.1002/hep.23836 PMID: 20799354
16. Russo AE, Torrisi E, Bevelacqua Y, Perrotta R, Libra M, McCubrey JA, et al. (2009) Melanoma: molecular pathogenesis and emerging target therapies (Review). Int J Oncol 34: 1481-1489. PMID: 19424565
17. Kolev VN, Wright QG, Vidal CM, Ring JE, Shapiro IM, Ricono J, et al. (2015) PI3K/mTOR dual inhibitor VS-5584 preferentially targets cancer stem cells. Cancer Res 75: 446-455. doi: 10.1158/0008-5472. CAN-14-1223 PMID: 25432176
18. Liu P, Cheng H, Roberts TM, Zhao JJ (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8: 627-644. doi: 10.1038/nrd2926 PMID: 19644473
19. Averous J, Fonseca BD, Proud CG (2008) Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. Oncogene 27: 1106-1113. PMID: 17724476
20. Leiter U, Schmid RM, Kaskel P, Peter RU, Krahn G (2000) Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma. Arch Dermatol Res 292: 225-232. PMID: 10867810
21. van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE, et al. (2006) The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 10: 389-399. PMID: 17097561
22. Populo H, Soares P, Lopes JM (2012) Insights into melanoma: targeting the mTOR pathway for therapeutics. Expert Opin Ther Targets 16: 689-705. doi: 10.1517/14728222.2012.691472 PMID: 22620498
23. Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149: 274-293. doi: 10.1016/j.cell.2012.03.017 PMID: 22500797
24. Guertin DA, Sabatini DM (2007) Defining the role of mTOR in cancer. Cancer Cell 12: 9-22. PMID: 17613433
25. Dienstmann R, Rodon J, Serra V, Tabernero J (2014) Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol Cancer Ther 13: 1021-1031. doi: 10.1158/1535- 7163.MCT-13-0639 PMID: 24748656
26. Sun SY (2013) mTOR kinase inhibitors as potential cancer therapeutic drugs. Cancer Lett 340: 1-8. doi: 10.1016/j.canlet.2013.06.017 PMID: 23792225