Abstract
Background: The introduction of Monoclonal Antibodies (mAbs) and small-molecule Tyrosine Kinase Inhibitors (TKIs) that target the Epidermal Growth Factor Receptor (EGFR), marks a huge step forward in the Pancreatic Cancer (PC) therapy. However, anti-EGFR therapy is found to be successful only in a fraction of patients. Although anti-EGFR agents have shown considerable clinical promise, a serious adverse event associated with anti- EGFR therapy has been challenging. At this juncture, there is still more to be done in the search for effective predictive markers with therapeutic applicability.
Methods: A focused literature search was conducted to summarize the existing evidence on anti-EGFR agents in pancreatic cancer therapy.
Results: This review discusses various anti-EGFR agents currently in use for PC therapy and potential adverse effects associated with it. Existing evidence on EGFR TKIs demonstrated better tolerant effects and outcomes with multiple toxic regimens. Anti-EGFR therapy in combination with chemotherapy is necessary to achieve the best clinical outcomes.
Conclusion: Future prospective studies on the identification of additional biological agents and novel anti-EGFR agents are warranted.
Keywords: Pancreatic cancer, EGFR, anti-EGFR agents, toxicity, resistance, chemotherapy.
Graphical Abstract
[http://dx.doi.org/10.1186/s13045-018-0616-2] [PMID: 29843755]
[http://dx.doi.org/10.1016/j.jaad.2005.10.010] [PMID: 17010747]
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b01040] [PMID: 30589553]
[http://dx.doi.org/10.4297/najms.2011.31] [PMID: 22540056]
[http://dx.doi.org/10.1016/S0973-6883(11)60112-6] [PMID: 25755309]
[http://dx.doi.org/10.1634/theoncologist.7-suppl_4-31] [PMID: 12202786]
[http://dx.doi.org/10.1097/01.NCC.0000281759.23823.82] [PMID: 17666986]
[http://dx.doi.org/10.1002/ijc.30648] [PMID: 28198009]
[http://dx.doi.org/10.1016/S0959-8049(96)00324-3] [PMID: 9166095]
[http://dx.doi.org/10.1200/JCO.1997.15.6.2403] [PMID: 9196156]
[http://dx.doi.org/10.1097/COC.0000000000000068] [PMID: 24685886]
[http://dx.doi.org/10.1038/sj.bjc.6604121] [PMID: 18059397]
[http://dx.doi.org/10.1200/JCO.2009.24.2446] [PMID: 19858379]
[http://dx.doi.org/10.1200/JCO.2005.04.1749] [PMID: 16446337]
[http://dx.doi.org/10.1080/15384047.2018.1433503] [PMID: 29658816]
[http://dx.doi.org/10.1007/s00280-010-1472-0] [PMID: 20927525]
[http://dx.doi.org/10.1186/s13014-015-0564-8] [PMID: 26670587]
[http://dx.doi.org/10.1001/jamaoncol.2018.2706] [PMID: 29860482]
[http://dx.doi.org/10.1007/s00280-017-3375-9] [PMID: 28702772]
[http://dx.doi.org/10.1080/07357900801918611] [PMID: 18798073]
[http://dx.doi.org/10.1097/00000658-199912000-00005] [PMID: 10615931]
[http://dx.doi.org/10.1093/jjco/hyx075] [PMID: 28541474]
[http://dx.doi.org/10.21037/jtd.2017.09.123] [PMID: 29268429]
[http://dx.doi.org/10.1177/1533034615585209] [PMID: 25987640]
[http://dx.doi.org/10.1200/jco.2015.33.15_suppl.tps4150]
[http://dx.doi.org/10.1016/j.ejca.2018.02.008] [PMID: 29549862]
[http://dx.doi.org/10.1093/annonc/mdy282.102]
[http://dx.doi.org/10.1634/theoncologist.2018-0878] [PMID: 30679315]
[http://dx.doi.org/10.1200/JCO.2006.09.0886] [PMID: 17538165]
[PMID: 14682118]
[http://dx.doi.org/10.1080/23723556.2015.1004969] [PMID: 27308503]
[http://dx.doi.org/10.1007/s11523-015-0403-8] [PMID: 26668065]
[http://dx.doi.org/10.3889/oamjms.2019.104] [PMID: 30894932]
[http://dx.doi.org/10.1159/000106064] [PMID: 17646699]
[http://dx.doi.org/10.1038/bjc.2011.396] [PMID: 21970876]
[http://dx.doi.org/10.1016/j.ejca.2016.12.032] [PMID: 28222309]
[http://dx.doi.org/10.3310/hta13suppl2/01] [PMID: 19804683]
[http://dx.doi.org/10.1200/jco.2011.29.4_suppl.238]
[http://dx.doi.org/10.1016/j.gendis.2014.10.002] [PMID: 25815366]
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0979] [PMID: 26251290]
[http://dx.doi.org/10.1186/s12885-016-2889-6] [PMID: 27871278]
[http://dx.doi.org/10.1016/j.ccr.2005.03.003] [PMID: 15837620]
[http://dx.doi.org/10.1016/j.neo.2014.06.004] [PMID: 25117978]
[http://dx.doi.org/10.1186/s12943-018-0793-1] [PMID: 29455669]
[PMID: 23393373]
[http://dx.doi.org/10.1097/CJI.0b013e3182562d76] [PMID: 22576341]
[http://dx.doi.org/10.3892/etm_00000047] [PMID: 22993543]
[http://dx.doi.org/10.3390/cells3020304] [PMID: 24758840]
[http://dx.doi.org/10.1016/j.ijrobp.2006.07.008] [PMID: 16965868]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0004] [PMID: 27435400]
[http://dx.doi.org/10.1053/j.seminoncol.2006.04.003] [PMID: 16890793]
[http://dx.doi.org/10.1038/sj.bjc.6604373] [PMID: 18506149]
[http://dx.doi.org/10.1007/s00210-014-0967-3] [PMID: 24643470]
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0038] [PMID: 21084261]
[http://dx.doi.org/10.18632/oncotarget.18834] [PMID: 28978069]
[http://dx.doi.org/10.1200/JCO.2006.07.9525] [PMID: 17452677]
[PMID: 22307557]
[http://dx.doi.org/10.1111/1523-1747.ep12510246] [PMID: 6177800]
[http://dx.doi.org/10.5539/cco.v6n2p45]
[http://dx.doi.org/10.1007/s10637-011-9651-3] [PMID: 21404106]
[http://dx.doi.org/10.1111/j.1349-7006.2010.01810.x] [PMID: 21175992]
[http://dx.doi.org/10.1200/JCO.2009.25.7550] [PMID: 20606093]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3753] [PMID: 16585207]
[http://dx.doi.org/10.1093/annonc/mdu176] [PMID: 24827134]
[PMID: 18505086]
[http://dx.doi.org/10.3748/wjg.v21.i8.2281] [PMID: 25741134]
[http://dx.doi.org/10.23736/S0026-4733.18.07512-0] [PMID: 29397631]
[http://dx.doi.org/10.1155/2018/8739473] [PMID: 30670929]
[http://dx.doi.org/10.1016/j.ejca.2014.04.008] [PMID: 24857345]
[http://dx.doi.org/10.1053/sonc.2003.50027] [PMID: 12644979]
[PMID: 16736981]
[http://dx.doi.org/10.1093/annonc/mdx343] [PMID: 28961832]
[http://dx.doi.org/10.1517/14728222.2011.648617] [PMID: 22239438]
[http://dx.doi.org/10.1159/000342203] [PMID: 23006507]
[http://dx.doi.org/10.1186/s12885-016-2482-z] [PMID: 27400734]
[http://dx.doi.org/10.1007/s10637-010-9619-8] [PMID: 21170759]
[http://dx.doi.org/10.1007/s13277-013-1306-x] [PMID: 24142531]
[http://dx.doi.org/10.2147/OTT.S124097] [PMID: 28203092]
[PMID: 30655893]
[http://dx.doi.org/10.18632/oncotarget.2231] [PMID: 25216528]
[http://dx.doi.org/10.1186/s40780-016-0060-9] [PMID: 27688901]
[http://dx.doi.org/10.1200/JCO.2008.20.0238] [PMID: 19307500]
[http://dx.doi.org/10.1056/NEJMoa1304369] [PMID: 24131140]
[PMID: 28513565]
[http://dx.doi.org/10.1093/annonc/mdx703] [PMID: 29462254]
[http://dx.doi.org/10.1200/JCO.2004.12.040] [PMID: 15226328]
[http://dx.doi.org/10.1097/ICO.0b013e318064584a] [PMID: 17667622]
[http://dx.doi.org/10.2174/1568009616666161013101657] [PMID: 27739365]
[http://dx.doi.org/10.1002/ar.20938]