Abstract
Background: Surgical resection of the lesion is the standard primary treatment of gastric cancer. Unfortunately, most patients are already in the advanced stage of the disease when they are diagnosed with gastric cancer. Alternative therapies, such as radiation therapy and chemotherapy, can achieve only very limited benefits. The emergence of cancer drug resistance has always been the major obstacle to the cure of tumors. The main goal of modern cancer pharmacology is to determine the underlying mechanism of anticancer drugs.
Objectives: Here, we mainly review the latest research results related to the mechanism of chemotherapy resistance in gastric cancer, the application of natural products in overcoming the chemotherapy resistance of gastric cancer, and the new strategies currently being developed to treat tumors based on immunotherapy and gene therapy.
Conclusion: The emergence of cancer drug resistance is the main obstacle in achieving alleviation and final cure for gastric cancer. Mixed therapies are considered to be a possible way to overcome chemoresistance. Natural products are the main resource for discovering new drugs specific for treating chemoresistance, and further research is needed to clarify the mechanism of natural product activity in patients.
Keywords: Gastric cancer, chemoresistance, chemotherapy, multidrug resistance, overcoming chemoresistance, natural products.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[http://dx.doi.org/10.1186/s40880-018-0293-0] [PMID: 29764518]
[http://dx.doi.org/10.1007/s11864-019-0654-1] [PMID: 31144054]
[http://dx.doi.org/10.1186/s12885-016-2772-5] [PMID: 27633381]
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1007/s11894-017-0575-8] [PMID: 28730504]
[http://dx.doi.org/10.1016/S1470-2045(13)70546-1] [PMID: 24314615]
[http://dx.doi.org/10.1016/j.bpg.2006.04.008] [PMID: 16997150]
[http://dx.doi.org/10.1093/jnci/djj071] [PMID: 16507831]
[http://dx.doi.org/10.3748/wjg.v20.i28.9600] [PMID: 25071358]
[http://dx.doi.org/10.3390/nu6114961] [PMID: 25389898]
[http://dx.doi.org/10.3389/fonc.2020.01526] [PMID: 33072546]
[http://dx.doi.org/10.1002/cncr.27550] [PMID: 22549558]
[http://dx.doi.org/10.1007/s00432-008-0474-3] [PMID: 18830628]
[http://dx.doi.org/10.3748/wjg.v22.i37.8283] [PMID: 27729735]
[http://dx.doi.org/10.1007/s10120-013-0259-5] [PMID: 23572188]
[http://dx.doi.org/10.1007/s12029-016-9912-7] [PMID: 28028765]
[PMID: 26807164]
[http://dx.doi.org/10.7326/0003-4819-151-2-200907210-00009] [PMID: 19620164]
[http://dx.doi.org/10.2174/13816128113196660731] [PMID: 24180402]
[http://dx.doi.org/10.1007/s10555-019-09803-7] [PMID: 31486976]
[http://dx.doi.org/10.3978/j.issn.2078-6891.2015.037] [PMID: 26487950]
[http://dx.doi.org/10.3748/wjg.v21.i37.10510] [PMID: 26457012]
[http://dx.doi.org/10.1245/s10434-015-4931-3] [PMID: 26530444]
[http://dx.doi.org/10.1016/S0140-6736(17)31827-5] [PMID: 28993052]
[http://dx.doi.org/10.1007/s10120-020-01058-4] [PMID: 32180056]
[PMID: 26408698]
[http://dx.doi.org/10.1016/j.molonc.2016.09.004] [PMID: 27720576]
[http://dx.doi.org/10.1007/s10120-017-0760-3] [PMID: 28801853]
[http://dx.doi.org/10.1038/nature12965] [PMID: 24476821]
[http://dx.doi.org/10.1001/jamaoncol.2018.0013] [PMID: 29543932]
[http://dx.doi.org/10.1186/s40425-019-0508-1] [PMID: 30717797]
[http://dx.doi.org/10.1007/s10120-018-0903-1] [PMID: 30515672]
[http://dx.doi.org/10.1007/s10120-018-00909-5] [PMID: 30911859]
[http://dx.doi.org/10.4049/jimmunol.176.5.3000] [PMID: 16493058]
[http://dx.doi.org/10.1007/s12026-011-8227-9] [PMID: 21717068]
[http://dx.doi.org/10.1038/s41591-018-0101-z] [PMID: 30013197]
[http://dx.doi.org/10.1016/S0140-6736(10)61121-X] [PMID: 20728210]
[http://dx.doi.org/10.3389/fonc.2020.584772] [PMID: 33425738]
[http://dx.doi.org/10.1007/s11912-019-0820-4] [PMID: 31236716]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3893] [PMID: 22751462]
[http://dx.doi.org/10.1111/j.1365-2559.2008.03021.x]
[http://dx.doi.org/10.1016/j.ejca.2018.01.079] [PMID: 29501977]
[http://dx.doi.org/10.1093/annonc/mdw350] [PMID: 27664260]
[http://dx.doi.org/10.1007/s10120-016-0622-4] [PMID: 27342689]
[http://dx.doi.org/10.1023/A:1008243606668] [PMID: 9093725]
[http://dx.doi.org/10.3389/fonc.2020.614907] [PMID: 33330111]
[http://dx.doi.org/10.1200/JCO.2008.19.1718] [PMID: 19332728]
[http://dx.doi.org/10.1093/annonc/mdp047] [PMID: 19474114]
[http://dx.doi.org/10.1056/NEJMc0911925] [PMID: 20200397]
[http://dx.doi.org/10.6004/jnccn.2016.0137] [PMID: 27697982]
[http://dx.doi.org/10.1016/S1470-2045(18)30791-5] [PMID: 30718072]
[http://dx.doi.org/10.1093/annonc/mdy502] [PMID: 30475956]
[http://dx.doi.org/10.1200/JCO.1988.6.10.1653] [PMID: 3049954]
[http://dx.doi.org/10.1038/nrc1074] [PMID: 12724731]
[http://dx.doi.org/10.1038/s41467-020-20260-7] [PMID: 33311518]
[http://dx.doi.org/10.1124/mol.58.5.920] [PMID: 11040038]
[http://dx.doi.org/10.1016/j.ctrv.2006.09.006] [PMID: 17084534]
[http://dx.doi.org/10.1053/ejso.2001.1234] [PMID: 11944952]
[http://dx.doi.org/10.3748/wjg.v10.i5.750] [PMID: 14991954]
[http://dx.doi.org/10.1200/JCO.2005.01.917] [PMID: 16145066]
[http://dx.doi.org/10.1159/000334545] [PMID: 22156447]
[http://dx.doi.org/10.1097/00001813-199607000-00010] [PMID: 8862723]
[http://dx.doi.org/10.1002/14651858.CD004064.pub4] [PMID: 28850174]
[http://dx.doi.org/10.3109/00498259609046718] [PMID: 9173680]
[http://dx.doi.org/10.1136/gut.2008.155861] [PMID: 19091831]
[http://dx.doi.org/10.1016/S1470-2045(20)30315-6] [PMID: 32682457]
[http://dx.doi.org/10.1016/S0140-6736(11)61873-4] [PMID: 22226517]
[http://dx.doi.org/10.1007/s10120-015-0581-1] [PMID: 26626800]
[http://dx.doi.org/10.1007/s10555-015-9576-y] [PMID: 26267802]
[http://dx.doi.org/10.1016/S1470-2045(14)70473-5] [PMID: 25439693]
[http://dx.doi.org/10.1007/s00280-007-0515-7] [PMID: 17522863]
[http://dx.doi.org/10.1200/JCO.2002.02.021] [PMID: 12454110]
[http://dx.doi.org/10.1186/s12885-019-6433-3] [PMID: 31852475]
[http://dx.doi.org/10.21873/anticanres.14030] [PMID: 32014941]
[http://dx.doi.org/10.2174/1871520615666150803125121] [PMID: 26234359]
[http://dx.doi.org/10.1007/s00280-005-0140-2] [PMID: 16465545]
[http://dx.doi.org/10.1093/annonc/mdq248] [PMID: 20494962]
[http://dx.doi.org/10.1038/nrclinonc.2016.15] [PMID: 26925958]
[http://dx.doi.org/10.1038/nrd1984] [PMID: 16518375]
[http://dx.doi.org/10.1038/nrc3342] [PMID: 22918414]
[http://dx.doi.org/10.1200/JCO.1999.17.3.1061] [PMID: 10071301]
[http://dx.doi.org/10.1146/annurev.med.53.082901.103929] [PMID: 11818492]
[http://dx.doi.org/10.2174/092986706777585077] [PMID: 16842198]
[http://dx.doi.org/10.1186/1756-9966-30-87] [PMID: 21943236]
[http://dx.doi.org/10.3390/ijms15023145] [PMID: 24566140]
[http://dx.doi.org/10.3389/fcell.2020.621428] [PMID: 33344463]
[http://dx.doi.org/10.1016/j.drup.2018.11.001] [PMID: 30471641]
[http://dx.doi.org/10.1038/nrc706] [PMID: 11902585]
[http://dx.doi.org/10.1111/bph.13422] [PMID: 26750865]
[http://dx.doi.org/10.1016/j.drup.2019.100663] [PMID: 31785545]
[http://dx.doi.org/10.1007/s00109-020-02015-5] [PMID: 33392633]
[http://dx.doi.org/10.1038/nm.3394] [PMID: 24202395]
[http://dx.doi.org/10.1177/1010428317698373] [PMID: 28459211]
[http://dx.doi.org/10.1002/iub.25] [PMID: 18380008]
[http://dx.doi.org/10.1111/jcmm.12216] [PMID: 24628949]
[http://dx.doi.org/10.3390/ijms18071434] [PMID: 28677634]
[PMID: 16391792]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-3040] [PMID: 17504982]
[http://dx.doi.org/10.1016/j.bbcan.2011.06.001] [PMID: 21741453]
[http://dx.doi.org/10.1038/nrc2803] [PMID: 20147901]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-3018] [PMID: 32321717]
[http://dx.doi.org/10.1080/07357907.2016.1267741] [PMID: 28102711]
[http://dx.doi.org/10.1016/j.clnu.2018.07.015] [PMID: 30075998]
[http://dx.doi.org/10.1186/s12885-018-5171-2] [PMID: 30558575]
[http://dx.doi.org/10.1200/JCO.1996.14.1.176] [PMID: 8558194]
[http://dx.doi.org/10.1200/JCO.1998.16.1.309] [PMID: 9440758]
[http://dx.doi.org/10.1002/ijc.22080] [PMID: 16736497]
[http://dx.doi.org/10.1111/j.1349-7006.2000.tb00866.x] [PMID: 10744051]
[http://dx.doi.org/10.1002/(SICI)1097-0142(19980501)82:9<1626::AID-CNCR5>3.0.CO;2-8] [PMID: 9576280]
[http://dx.doi.org/10.1038/nrc1368] [PMID: 15170448]
[http://dx.doi.org/10.1186/1471-2407-10-367] [PMID: 20618998]
[http://dx.doi.org/10.1042/BSR20193045] [PMID: 31793989]
[http://dx.doi.org/10.1186/s12943-020-01185-7] [PMID: 32192494]
[http://dx.doi.org/10.1016/j.biopha.2018.01.130] [PMID: 29710482]
[http://dx.doi.org/10.1186/1471-2407-14-932] [PMID: 25496320]
[http://dx.doi.org/10.3892/or.2016.4771] [PMID: 27121324]
[http://dx.doi.org/10.1002/jcb.29370] [PMID: 31478258]
[http://dx.doi.org/10.1098/rsob.190068] [PMID: 31551012]
[http://dx.doi.org/10.26355/eurrev_201904_17554] [PMID: 31002130]
[http://dx.doi.org/10.1016/j.biopha.2018.09.181] [PMID: 30372881]
[http://dx.doi.org/10.3892/mmr.2017.8184] [PMID: 29207111]
[http://dx.doi.org/10.1002/cam4.1055] [PMID: 28544609]
[http://dx.doi.org/10.3892/or.2017.5415] [PMID: 28184940]
[http://dx.doi.org/10.1007/s00109-017-1600-y] [PMID: 29098316]
[http://dx.doi.org/10.1186/s12943-019-0969-3] [PMID: 30927924]
[http://dx.doi.org/10.1186/s12935-019-0737-x] [PMID: 30733646]
[http://dx.doi.org/10.2174/13894501113149990183] [PMID: 23834156]
[http://dx.doi.org/10.3892/mmr.2013.1384] [PMID: 23525256]
[PMID: 24817940]
[http://dx.doi.org/10.1002/ijc.23501] [PMID: 18449891]
[http://dx.doi.org/10.1038/cddis.2015.123] [PMID: 25996293]
[http://dx.doi.org/10.1038/onc.2013.297] [PMID: 23893241]
[http://dx.doi.org/10.12659/MSM.896633] [PMID: 27353653]
[http://dx.doi.org/10.1016/j.gene.2015.11.013] [PMID: 26589846]
[http://dx.doi.org/10.1016/j.canlet.2017.09.035] [PMID: 28965855]
[http://dx.doi.org/10.3892/etm.2017.5354] [PMID: 29375703]
[http://dx.doi.org/10.1002/ijc.25260] [PMID: 20162574]
[http://dx.doi.org/10.1159/000438524] [PMID: 26513239]
[http://dx.doi.org/10.1177/1535370217728460]
[http://dx.doi.org/10.1038/s41419-018-0950-x] [PMID: 30341283]
[http://dx.doi.org/10.1124/mol.105.011015] [PMID: 15901850]
[http://dx.doi.org/10.1179/joc.2005.17.2.215] [PMID: 15920909]
[http://dx.doi.org/10.3892/etm.2016.3589] [PMID: 27698692]
[http://dx.doi.org/10.1007/s00018-016-2362-3] [PMID: 27622244]
[http://dx.doi.org/10.2174/1574892816666210218220943]
[http://dx.doi.org/10.1016/j.fct.2009.01.037] [PMID: 19425231]
[http://dx.doi.org/10.1186/s12885-019-5957-x] [PMID: 31351462]
[http://dx.doi.org/10.7150/jca.34773] [PMID: 31897241]
[http://dx.doi.org/10.1016/j.lfs.2020.117280] [PMID: 31926239]
[http://dx.doi.org/10.3892/ijmm.2020.4520] [PMID: 32323738]
[http://dx.doi.org/10.1016/j.phymed.2018.05.012] [PMID: 30466628]
[http://dx.doi.org/10.1016/j.bmcl.2015.08.005] [PMID: 26283511]
[http://dx.doi.org/10.3748/wjg.v9.i9.1930] [PMID: 12970878]
[http://dx.doi.org/10.4314/ajtcam.v11i1.28] [PMID: 24653574]
[http://dx.doi.org/10.1080/01635581.2010.509837] [PMID: 20924970]
[http://dx.doi.org/10.3892/or.2012.1772] [PMID: 22552443]
[http://dx.doi.org/10.1021/bp034143b] [PMID: 14763870]
[http://dx.doi.org/10.3748/wjg.v20.i27.8971] [PMID: 25083070]
[http://dx.doi.org/10.1158/1940-6207.CAPR-14-0172] [PMID: 25586902]
[http://dx.doi.org/10.1016/j.canlet.2004.10.009] [PMID: 15911108]
[http://dx.doi.org/10.3892/or_00001021] [PMID: 21042755]
[http://dx.doi.org/10.2174/1871520616666151111115443] [PMID: 26555611]
[http://dx.doi.org/10.3390/molecules23123175] [PMID: 30513793]
[http://dx.doi.org/10.3389/fphar.2018.01150] [PMID: 30405404]
[http://dx.doi.org/10.3390/molecules190812349] [PMID: 25153862]
[http://dx.doi.org/10.22038/IJBMS.2017.8676] [PMID: 28656087]
[http://dx.doi.org/10.2174/138955709788167592] [PMID: 19456286]
[http://dx.doi.org/10.1186/1749-8546-6-27] [PMID: 21777476]
[PMID: 32277648]
[http://dx.doi.org/10.1016/j.biopha.2020.110245] [PMID: 32454290]
[http://dx.doi.org/10.1007/s11626-016-0044-y] [PMID: 27142767]
[http://dx.doi.org/10.3389/fphar.2020.616251] [PMID: 33362566]
[http://dx.doi.org/10.1016/j.tox.2013.05.015] [PMID: 23770416]
[http://dx.doi.org/10.1155/2020/9396512] [PMID: 32149146]
[http://dx.doi.org/10.7785/tcrt.2012.500434] [PMID: 24988056]
[http://dx.doi.org/10.1186/s12967-017-1151-6] [PMID: 28241766]
[http://dx.doi.org/10.3892/ol.2017.6380] [PMID: 28789432]
[http://dx.doi.org/10.3892/mmr.2014.2157] [PMID: 24736991]
[http://dx.doi.org/10.1016/j.phymed.2016.10.018] [PMID: 27912880]
[http://dx.doi.org/10.7150/jca.13548] [PMID: 26918059]
[http://dx.doi.org/10.3892/mmr.2014.2452] [PMID: 25109410]
[http://dx.doi.org/10.1142/S0192415X21500245] [PMID: 33641654]
[http://dx.doi.org/10.3892/or.2014.3669] [PMID: 25502212]
[http://dx.doi.org/10.3892/or.2014.3550] [PMID: 25333894]
[http://dx.doi.org/10.1016/j.bbrc.2020.07.045] [PMID: 32800561]
[http://dx.doi.org/10.1111/1750-3841.14372] [PMID: 30468256]
[http://dx.doi.org/10.1016/j.phymed.2013.09.007] [PMID: 24176842]
[http://dx.doi.org/10.1016/j.phymed.2017.02.008] [PMID: 28478808]
[http://dx.doi.org/10.1016/j.prp.2020.152995] [PMID: 32402536]
[http://dx.doi.org/10.3390/nu10101490] [PMID: 30322062]
[http://dx.doi.org/10.1016/j.fct.2019.04.012] [PMID: 30991130]
[http://dx.doi.org/10.1039/C4NP00080C] [PMID: 25347695]
[http://dx.doi.org/10.3892/etm.2018.6067] [PMID: 29805515]
[http://dx.doi.org/10.1038/s41419-018-0581-2] [PMID: 29760378]
[http://dx.doi.org/10.1159/000488273] [PMID: 29558748]
[http://dx.doi.org/10.2147/OTT.S275327] [PMID: 33116644]
[http://dx.doi.org/10.1016/j.sjbs.2018.01.012] [PMID: 30108441]
[http://dx.doi.org/10.1016/j.canlet.2017.11.037] [PMID: 29199005]
[http://dx.doi.org/10.7314/APJCP.2016.17.4.1817] [PMID: 27221858]
[http://dx.doi.org/10.1016/j.bcp.2019.07.008] [PMID: 31301277]
[http://dx.doi.org/10.1055/s-2003-38483] [PMID: 12677527]
[http://dx.doi.org/10.1016/S0006-2952(02)01446-6] [PMID: 12473381]
[http://dx.doi.org/10.1055/s-0033-1360334] [PMID: 24493631]
[PMID: 9816216]
[http://dx.doi.org/10.1002/ptr.5023] [PMID: 23824931]
[http://dx.doi.org/10.1093/annonc/mdq390] [PMID: 20688844]
[http://dx.doi.org/10.1146/annurev.nutr.21.1.381] [PMID: 11375442]
[http://dx.doi.org/10.3892/ijmm.2016.2625] [PMID: 27278820]
[http://dx.doi.org/10.1080/10408690490464960] [PMID: 15462129]
[http://dx.doi.org/10.4161/auto.7.9.15863] [PMID: 21610320]
[http://dx.doi.org/10.1002/jcb.21977] [PMID: 19009557]
[http://dx.doi.org/10.1093/ecam/neq053] [PMID: 21792362]
[http://dx.doi.org/10.1016/j.tiv.2011.11.015] [PMID: 22222411]
[http://dx.doi.org/10.1007/s00535-008-2184-7] [PMID: 18600388]
[http://dx.doi.org/10.1016/j.fct.2012.06.035] [PMID: 22750388]
[http://dx.doi.org/10.1002/tox.22623] [PMID: 30152185]
[http://dx.doi.org/10.3390/molecules21101286] [PMID: 27681719]
[http://dx.doi.org/10.2174/0929867322666150812145435] [PMID: 26264923]
[http://dx.doi.org/10.1016/j.biopha.2018.03.110] [PMID: 29635130]
[http://dx.doi.org/10.3390/molecules23020209] [PMID: 29364834]
[http://dx.doi.org/10.1016/S0304-3835(96)04443-6] [PMID: 9020919]
[http://dx.doi.org/10.2147/IJN.S170862] [PMID: 30233175]
[http://dx.doi.org/10.1016/j.tiv.2005.06.048] [PMID: 16289744]
[http://dx.doi.org/10.3892/ijo.2017.4134] [PMID: 29048624]
[http://dx.doi.org/10.1038/s41419-018-0658-y] [PMID: 29844404]
[http://dx.doi.org/10.1016/j.biopha.2017.06.095] [PMID: 28715876]
[http://dx.doi.org/10.1021/acs.jafc.6b04815] [PMID: 27935709]
[http://dx.doi.org/10.1016/j.abb.2020.108314] [PMID: 32088220]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00975] [PMID: 28074653]
[http://dx.doi.org/10.4161/cbt.8.14.8720] [PMID: 19448398]
[PMID: 11396178]
[http://dx.doi.org/10.3892/or.2011.1410] [PMID: 21811763]
[http://dx.doi.org/10.1002/biof.1068] [PMID: 23303705]
[http://dx.doi.org/10.3892/or.2013.2875] [PMID: 24284968]
[http://dx.doi.org/10.1002/ardp.200900319] [PMID: 20726007]
[http://dx.doi.org/10.4196/kjpp.2011.15.1.1] [PMID: 21461234]
[http://dx.doi.org/10.1186/s13046-017-0513-5] [PMID: 28359291]
[http://dx.doi.org/10.1016/j.redox.2018.11.019] [PMID: 30590310]
[http://dx.doi.org/10.7314/APJCP.2014.15.18.7747] [PMID: 25292057]
[http://dx.doi.org/10.1016/j.carbpol.2017.05.045] [PMID: 28732851]
[http://dx.doi.org/10.1038/srep11853] [PMID: 26149967]
[http://dx.doi.org/10.1016/j.bbrc.2004.02.158] [PMID: 15044093]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4257] [PMID: 17440100]
[http://dx.doi.org/10.3748/wjg.v16.i32.4039] [PMID: 20731017]
[http://dx.doi.org/10.1016/j.semcancer.2016.02.001] [PMID: 26853158]