[Advances in the Research of Autophagy in EGFR-TKI Treatment and Resistance  in Lung Cancer].
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic. On one hand, autophagy induced by EGFR-TKI acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR-TKI. On the other hand, a high level of autophagy after treatment of EGFR-TKI can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR-TKI with autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficiency of EGFR-TKI in the treatment of cancer patients. Here we summarized the signaling pathways involved in EGFR-TKI induced autophagy, and reviewed the roles of autophagy in the treatment and chemoresistance of EGFR-TKI treatment in lung cancer.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Qicheng
Q
Zhang
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Ke
K
Xu
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
Autophagy. 2008 Jul;4(5):641-9
18398293
Mol Clin Oncol. 2014 Jan;2(1):8-12
24649300
Biochem Pharmacol. 2009 Sep 1;78(5):460-8
19427302
Cell. 2010 Jun 25;141(7):1117-34
20602996
PLoS One. 2012;7(10):e48532
23119048
Oncotarget. 2014 Jul 15;5(13):4765-78
24946858
Clin Lung Cancer. 2010 Sep 1;11(5):E1-4
20837450
Clin Cancer Res. 2008 Nov 15;14(22):7519-25
19010870
PLoS Med. 2007 Oct;4(10):1669-79; discussion 1680
17973572
Autophagy. 2008 Aug;4(6):740-3
18567941
Oncotarget. 2014 Sep 15;5(17):7328-41
25193862
Genes Dev. 2004 Aug 15;18(16):1926-45
15314020
J Thorac Oncol. 2013 Jun;8(6):693-702
23575415
Nat Med. 2012 Mar 18;18(4):521-8
22426421
Nature. 2006 May 25;441(7092):424-30
16724053
J BUON. 2014 Apr-Jun;19(2):466-73
24965408
Cancer Biol Ther. 2011 Jan 15;11(2):157-68
21228626
Cancer Cell. 2008 May;13(5):385-93
18455122
Breast Cancer Res. 2012 Jul 12;14(4):R104
22788954
Oncogene. 2004 May 13;23(22):3898-904
15064741
Cell Death Dis. 2013 Oct 10;4:e838
24113172
Cell Cycle. 2014;13(1):42-51
24335351
N Engl J Med. 2011 Mar 10;364(10):947-55
21388312
Genes Dev. 2011 Oct 1;25(19):1999-2010
21979913
Clin Cancer Res. 2013 Apr 15;19(8):2240-7
23470965
World J Clin Oncol. 2011 Nov 10;2(11):367-76
22087435
J Clin Invest. 2015 Jan;125(1):42-6
25654549
Lab Invest. 2013 Oct;93(10):1137-46
23938604
Nat Cell Biol. 2004 Dec;6(12):1221-8
15558033
N Engl J Med. 2005 Feb 24;352(8):786-92
15728811
Curr Opin Cell Biol. 2005 Apr;17(2):158-66
15780592
Semin Cancer Biol. 2013 Aug;23(4):252-61
23810837
Cancer Manag Res. 2015 Sep 11;7:291-9
26392787
Biochim Biophys Acta. 2010 Mar;1804(3):433-9
20005306
Science. 2004 Jun 4;304(5676):1500-2
15131264
J Pathol. 2014 Oct;234(2):277-88
24687913
J Thorac Oncol. 2012 Oct;7(10):1602-8
22878749
Clin Cancer Res. 2006 Dec 15;12(24):7242-51
17189395
Clin Cancer Res. 2007 Jun 1;13(11):3431; author reply 3431-2
17545553
CA Cancer J Clin. 2015 Mar;65(2):87-108
25651787
Expert Rev Anticancer Ther. 2013 Oct;13(10):1219-28
24134423
Cancer Res. 2012 Sep 1;72(17):4294-9
22915758
Cancer Biol Ther. 2011 Jun 15;11(12):1017-27
21508666
Cancer Lett. 2011 Nov 28;310(2):207-15
21807458
Clin Cancer Res. 2015 Feb 1;21(3):498-504
25165101
Mol Cell Biol. 2012 Jan;32(1):2-11
22025673
Int J Biochem Cell Biol. 2013 May;45(5):921-4
23420005
Cell. 2013 Sep 12;154(6):1269-84
24034250
PLoS One. 2013 Oct 11;8(10):e76503
24146879
Lung Cancer. 2013 Sep;81(3):354-61
23769318
Br J Cancer. 2010 Aug 24;103(5):622-8
20683448
Int J Oncol. 2016 Jun;48(6):2558-66
27035631
Science. 2012 Nov 16;338(6109):956-9
23112296
Nat Med. 2013 Nov;19(11):1389-400
24202392
Biochimie. 2008 Feb;90(2):313-23
17928127
Tumour Biol. 2014 Dec;35(12):11701-9
25293518
Cancer Biol Ther. 2012 Dec;13(14):1417-24
22954701
Curr Opin Genet Dev. 2009 Feb;19(1):12-7
19185485
Oncotarget. 2013 Dec;4(12):2512-22
24318272
J Biol Chem. 2009 Jan 2;284(1):334-44
18974095
Tumour Biol. 2012 Feb;33(1):85-94
21986964
Biochim Biophys Acta. 2009 Sep;1793(9):1516-23
19167434
Nat Cell Biol. 2010 Sep;12(9):814-22
20811353
Int J Cancer. 2009 Apr 15;124(8):1778-84
19117057
PLoS One. 2011 Jan 31;6(1):e14614
21297943
J Exp Med. 2015 Jun 29;212(7):979-90
26101267
Ann Oncol. 2013 Aug;24(8):2080-7
23559152
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5
18227510
Science. 2002 Jul 5;297(5578):63-4
12098689
Toxicol Appl Pharmacol. 2013 Nov 1;272(3):736-45
23917044
Nat Rev Mol Cell Biol. 2007 Sep;8(9):741-52
17717517
PLoS One. 2011;6(6):e18691
21655094
Cancer Res. 2006 Jul 1;66(13):6861-70
16818664