title: Untangling knots between autophagic targets and candidate drugs, in cancer therapy.
abstract: Autophagy is an evolutionarily conserved lysosomal mechanism implicated in a wide variety of pathological processes, such as cancer. Autophagy can be regulated by a limited number of autophagy-related genes (Atgs) such as oncogenic Bcl-2/Bcl-XL , mTORC1, Akt and PI3KCI, and tumour suppressive proteins PI3KCIII, Beclin-1, Bif-1, p53, DAPKs, PTEN and UVRAG, which play their crucial roles in regulating autophagy-related cancer. As autophagy has a dual role in cancer cells, with tumour-promoting and tumour-suppressing properties, it has become an attractive target for a series of emerging small molecule drugs. In this review, we reveal new discoveries of related small molecules or chemical compounds that can regulate autophagic pathways and lead to pro-death or pro-survival autophagy, in different types of cancer. We discuss the knots between autophagic targets and candidate drugs, in the hope of shedding new light on exploiting new anti-tumour small molecule drugs for future cancer therapy.
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors: Tao
authors: T
authors: Xie
authors: Si-Jia
authors: SJ
authors: Li
authors: Ming-Rui
authors: MR
authors: Guo
authors: Yue
authors: Y
authors: Wu
authors: Hang-Yu
authors: HY
authors: Wang
authors: Ke
authors: K
authors: Zhang
authors: Xue
authors: X
authors: Zhang
authors: Liang
authors: L
authors: Ouyang
authors: Jie
authors: J
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
references: Int J Biochem Cell Biol. 2003 May;35(5):553-61
references: 12672448
references: Biochim Biophys Acta. 2013 Aug;1831(8):1322-34
references: 23707264
references: Anticancer Res. 2009 Apr;29(4):1449-57
references: 19414401
references: Phytomedicine. 2013 Aug 15;20(11):1013-22
references: 23746959
references: Nature. 2007 Jun 28;447(7148):1121-5
references: 17589504
references: Chem Biol Interact. 2013 Sep 5;205(1):20-8
references: 23774672
references: PLoS One. 2013;8(2):e56679
references: 23441212
references: Apoptosis. 2014 Oct;19(10):1527-31
references: 25023961
references: Ann Intern Med. 2006 Mar 7;144(5):337-43
references: 16520474
references: Toxicol Lett. 2012 Aug 3;212(3):252-61
references: 22721804
references: Cell Biochem Funct. 2013 Oct;31(7):566-74
references: 23307628
references: Cancer Biol Ther. 2011 Sep 15;12(6):549-55
references: 21738008
references: Neoplasma. 2014;61(2):186-92
references: 24299314
references: J Clin Invest. 2010 Apr;120(4):1310-23
references: 20200450
references: Int J Oncol. 2012 Oct;41(4):1381-6
references: 22895785
references: Cancer Lett. 2014 Mar 28;344(2):239-59
references: 24280585
references: PLoS One. 2013;8(1):e54044
references: 23326571
references: Leukemia. 2014 Apr;28(4):739-48
references: 23892718
references: Exp Biol Med (Maywood). 2014 Jan;239(1):33-44
references: 24231340
references: Biochim Biophys Acta. 2013 Dec;1833(12):2856-2865
references: 23872419
references: J Biol Chem. 2013 Jun 21;288(25):18249-59
references: 23677989
references: FEBS J. 2011 Feb;278(3):403-13
references: 21182587
references: Autophagy. 2013 May;9(5):714-29
references: 23519090
references: Clin Cancer Res. 2011 Aug 15;17(16):5353-66
references: 21690574
references: Mar Drugs. 2013 Sep 17;11(9):3500-16
references: 24048269
references: Chin J Cancer. 2013 Mar;32(3):113-20
references: 22835386
references: Biomed Environ Sci. 2013 Nov;26(11):902-11
references: 24331535
references: J Cell Biochem. 2013 Dec;114(12):2643-53
references: 23794518
references: Biochem Biophys Res Commun. 2011 Sep 23;413(2):311-7
references: 21889492
references: Cell. 2008 Jan 11;132(1):27-42
references: 18191218
references: Arch Ital Biol. 2012 Jun-Sep;150(2-3):194-217
references: 23165879
references: Biochem Pharmacol. 2012 Nov 1;84(9):1154-63
references: 22902833
references: J Biol Chem. 2010 Sep 24;285(39):29989-97
references: 20656687
references: Phytochemistry. 2013 Oct;94:211-9
references: 23810286
references: J Hepatol. 2012 Jun;56(6):1343-50
references: 22322234
references: J Nutr Biochem. 2012 Aug;23(8):900-7
references: 21840189
references: Mol Cancer Ther. 2013 Apr;12(4):448-59
references: 23395885
references: Nat Cell Biol. 2008 Jun;10(6):637-9
references: 18521069
references: Br J Cancer. 2013 Jul 9;109(1):164-71
references: 23799852
references: Autophagy. 2013 Jul;9(7):1057-68
references: 23670030
references: Int J Biochem Cell Biol. 2012 Nov;44(11):1813-24
references: 22750415
references: EMBO Rep. 2008 Sep;9(9):859-64
references: 18704115
references: Org Lett. 2013 Aug 2;15(15):3918-21
references: 23869546
references: Nature. 2000 Nov 23;408(6811):488-92
references: 11100732
references: Oncol Rep. 2012 Feb;27(2):461-6
references: 21993902
references: Biochim Biophys Acta. 2013 Sep;1833(9):2057-69
references: 23639289
references: J Biol Chem. 2014 Apr 11;289(15):10607-19
references: 24599950
references: Biochim Biophys Acta. 2014 Jan;1840(1):1-9
references: 23962629
references: Anticancer Res. 2014 Feb;34(2):631-7
references: 24510992
references: FEBS Lett. 2010 Aug 20;584(16):3519-24
references: 20638385
references: Blood. 2009 Apr 2;113(14):3276-86
references: 19196867
references: J Cell Physiol. 2011 Mar;226(3):822-31
references: 20857426
references: J Pharm Pharmacol. 2012 Jan;64(1):146-53
references: 22150682
references: Cell Death Dis. 2013 Oct 31;4:e891
references: 24176849
references: Int J Mol Med. 2013 Jun;31(6):1449-56
references: 23588698
references: PLoS One. 2012;7(10):e48532
references: 23119048
references: Free Radic Biol Med. 2013 Dec;65:402-410
references: 23872397
references: Int J Biochem Cell Biol. 2011 Sep;43(9):1263-6
references: 21640844
references: Int J Oncol. 2013 Dec;43(6):1943-50
references: 24141596
references: J Biol Chem. 2012 May 4;287(19):15661-71
references: 22433868
references: Cell Death Dis. 2012 Nov 29;3:e431
references: 23190603
references: Cell Res. 2014 Jan;24(1):24-41
references: 24366339
references: PLoS One. 2013 Oct 10;8(10):e76340
references: 24130769
references: Mol Cancer Ther. 2012 Dec;11(12):2610-20
references: 23041544
references: Cell Death Differ. 2011 Apr;18(4):571-80
references: 21311563
references: J Mol Med (Berl). 2013 Apr;91(4):473-83
references: 23052483
references: Mol Cell Biochem. 2014 Jan;385(1-2):265-75
references: 24104452
references: Acta Pharmacol Sin. 2010 Sep;31(9):1154-64
references: 20694022
references: Toxicol Appl Pharmacol. 2013 Jul 15;270(2):122-8
references: 23624174
references: Sci Signal. 2010 Nov 09;3(147):ra81
references: 21062993
references: Pancreas. 2012 Oct;41(7):1039-47
references: 22647733
references: J Pharmacol Sci. 2012;118(4):423-32
references: 22466960
references: Lung Cancer. 2013 Sep;81(3):354-361
references: 23769318
references: Cancer Lett. 2011 Jan 28;300(2):105-14
references: 21036469
references: Br J Cancer. 2014 Feb 18;110(4):899-907
references: 24434432
references: Cancer Lett. 2013 Aug 19;336(2):370-8
references: 23567646
references: Oxid Med Cell Longev. 2013;2013:596496
references: 24379902
references: PLoS One. 2013 Oct 11;8(10):e76503
references: 24146879
references: Autophagy. 2005 Apr;1(1):1-10
references: 16874026
references: Nat Cell Biol. 2006 Jul;8(7):688-99
references: 16799551
references: Cancer Res. 2010 Feb 1;70(3):1042-52
references: 20103647
references: Cancer Biol Ther. 2011 Jun 15;11(12):1017-27
references: 21508666
references: Anticancer Res. 2013 May;33(5):1845-51
references: 23645729
references: Nat Cell Biol. 2008 Jun;10(6):676-87
references: 18454141
references: Cancer. 2012 Nov 15;118(22):5560-71
references: 22517429
references: PLoS One. 2013;8(1):e54346
references: 23349858
references: J Thorac Oncol. 2013 Jun;8(6):693-702
references: 23575415
references: Anticancer Drugs. 2012 Jun;23(5):494-504
references: 22391460
references: Cell Death Differ. 2009 Jul;16(7):1018-29
references: 19390558
references: Glycobiology. 2012 Sep;22(9):1245-55
references: 22692046
references: BMC Cancer. 2013 Mar 22;13:147
references: 23522185
references: Cell Biochem Biophys. 2013 Jul;66(3):567-87
references: 23300026
references: Tumour Biol. 2013 Aug;34(4):2367-78
references: 23580181
references: Trends Cell Biol. 2010 Jun;20(6):355-62
references: 20356743
references: Biochem Pharmacol. 2013 Apr 1;85(7):913-26
references: 23348250
references: Cancer Sci. 2012 Apr;103(4):684-90
references: 22192169
references: Int J Biochem Cell Biol. 2013 May;45(5):921-4
references: 23420005
references: Biochem Pharmacol. 2014 Jun 15;89(4):477-89
references: 24792437
references: Int J Oncol. 2012 Oct;41(4):1431-42
references: 22858649
references: Nat Cell Biol. 2002 Sep;4(9):648-57
references: 12172553
references: Br J Pharmacol. 2011 Sep;164(2b):731-42
references: 21418191
references: PLoS One. 2013 Sep 09;8(9):e72882
references: 24039814
references: Nat Cell Biol. 2010 Sep;12(9):814-22
references: 20811353
references: Cancer Lett. 2013 Oct 28;340(1):51-62
references: 23811287
references: Oncol Rep. 2013 Feb;29(2):430-6
references: 23151908
references: Apoptosis. 2012 Apr;17(4):325-34
references: 22170404
references: Int J Oncol. 2012 Jun;40(6):1929-40
references: 22367066
references: J Biol Chem. 2008 Sep 12;283(37):25596-605
references: 18628207
references: Apoptosis. 2013 Mar;18(3):337-46
references: 23238993
references: Leukemia. 2012 Nov;26(11):2336-42
references: 22614243
references: J Bioenerg Biomembr. 2012 Feb;44(1):51-60
references: 22318357
references: J Clin Invest. 2009 May;119(5):1109-23
references: 19363292
references: Nat Cell Biol. 2009 Apr;11(4):468-76
references: 19270693
references: Pancreas. 2013 Jul;42(5):829-35
references: 23429496
references: J Cell Physiol. 2013 Feb;228(2):292-7
references: 22777740
references: Mol Biol Rep. 2013 Oct;40(10):5645-55
references: 24065522
references: Chem Biol Interact. 2014 Feb 5;208:47-57
references: 24291674
references: Autophagy. 2008 Jul;4(5):629-40
references: 18376138
references: Mol Biol Cell. 2008 Dec;19(12):5360-72
references: 18843052
references: Apoptosis. 2014 Aug;19(8):1177-89
references: 24850099
references: J Cell Biol. 2010 Sep 6;190(5):881-92
references: 20819940
references: Int J Oncol. 2012 Sep;41(3):1036-42
references: 22684338
references: Pharmacology. 2012;89(5-6):247-55
references: 22507894
references: Biochem Soc Trans. 2010 Dec;38(6):1469-73
references: 21118109
references: Autophagy. 2009 Jul;5(5):727-8
references: 19363300
references: Biol Pharm Bull. 2011;34(8):1264-72
references: 21804216
references: Mol Cancer. 2013 Dec 23;12(1):171
references: 24359639
references: Nat Cell Biol. 2007 Oct;9(10):1142-51
references: 17891140
references: Int J Oncol. 2013 Nov;43(5):1413-9
references: 24026338
references: Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E592-602
references: 18765678
references: Biochem Pharmacol. 2014 May 15;89(2):197-209
references: 24630927
references: Mol Biol Cell. 2009 Apr;20(7):1992-2003
references: 19225151
references: Toxicol Mech Methods. 2012 Sep;22(7):512-9
references: 22519831
references: FEBS Lett. 2010 Apr 2;584(7):1287-95
references: 20083114
references: Autophagy. 2011 Jun;7(6):565-71
references: 21099252
references: Curr Opin Cell Biol. 2010 Apr;22(2):181-5
references: 20044243
references: Cancer Lett. 2013 Sep 1;337(2):254-65
references: 23664889
references: J Cell Sci. 2003 May 1;116(Pt 9):1679-88
references: 12665549
references: Cancer Res. 2010 Oct 15;70(20):8097-107
references: 20876803
references: Biochem Biophys Res Commun. 2012 Jul 13;423(4):826-31
references: 22713463
references: Oncol Rep. 2012 Apr;27(4):1128-34
references: 22200845
references: Oncol Rep. 2013 May;29(5):2072-8
references: 23468088
references: Eur J Nutr. 2013 Dec;52(8):1949-58
references: 23389114
references: Cell Death Dis. 2013 Jun 13;4:e664
references: 23764845
references: Cell Death Dis. 2013 Oct 31;4:e892
references: 24176850
references: J Cell Physiol. 2013 Jun;228(6):1314-22
references: 23168911
references: Carcinogenesis. 2012 Nov;33(11):2190-8
references: 22869602
references: J Cell Biochem. 2013 Jan;114(1):192-203
references: 22903547
references: J Cell Biol. 2000 Oct 16;151(2):263-76
references: 11038174
references: Cell Signal. 2012 Aug;24(8):1722-32
references: 22560876
references: Autophagy. 2009 Feb;5(2):173-83
references: 19066447