Abstract
The study aimed to comprehend the molecular mechanisms and pathophysiology of pancreatic cancer with an emphasis on the advances in treatment options and the use of natural products as anticancer agents. The study involved a literature survey using PubMed, Web of Science and Google scholar database. The literature search was done using keywords “Pancreatic cancer”, “Chemotherapy”, “Mutations”, and “Natural compounds”. 266 articles were studied of which 201 were taken into consideration based on relevance to the topic. Pancreatic cancer is associated with mutations of CDKN2A (encoding p16), KRAS, TP53 and SMAD4. MAPK, PI3K-AKT, and TGF- β pathway dysfunction also led to pancreatic cancer. Current clinical trial activities in pancreatic cancer target angiogenesis, surface receptors, cell cycle, DNA damage response, etc. Studies have shown that combining surgical resection with adjuvant chemotherapy increases survival rates in patients. New treatment options are on the rise for this cancer type, which is perioperative or neo-adjuvant therapy. Gemcitabine as a single treatment agent in pancreatic cancer has shown promising response with chemotherapy regimens using two combinations- Folfirinox and Gemcitabine/Nab-Paclitaxel giving a better response rate. Numerous natural substances, including curcumin, aloe vera, and taxol, which suppress oxidative stress, angiogenesis, JAK2 STAT3 pathways, and enhanced natural killer cell activity, have been explored as potential treatments for pancreatic cancer. With pancreatic cancer having a poor prognosis, investigations to comprehend its molecular underpinnings and research on natural chemicals could lead to the development of safer treatment alternatives with enhanced survival rates for pancreatic cancer patients.
Graphical Abstract
[http://dx.doi.org/10.1016/S0140-6736(16)00141-0] [PMID: 26830752]
[http://dx.doi.org/10.1038/nrc949] [PMID: 12459728]
[PMID: 17625148]
[http://dx.doi.org/10.4161/cbt.307] [PMID: 12642681]
[http://dx.doi.org/10.1016/S0140-6736(04)15841-8] [PMID: 15051286]
[http://dx.doi.org/10.14740/wjon1166] [PMID: 30834048]
[http://dx.doi.org/10.1056/NEJMra0901557] [PMID: 20427809]
[http://dx.doi.org/10.1001/jama.2009.886] [PMID: 19549972]
[http://dx.doi.org/10.1038/bjc.2012.111] [PMID: 22805322]
[http://dx.doi.org/10.1016/j.bpg.2005.10.001] [PMID: 16549324]
[http://dx.doi.org/10.1093/jnci/djp020] [PMID: 19276450]
[http://dx.doi.org/10.1016/S0304-4165(99)00183-X] [PMID: 10580143]
[http://dx.doi.org/10.1038/nrdp.2016.22] [PMID: 27158978]
[PMID: 12097290]
[http://dx.doi.org/10.1111/j.1399-0004.2010.01425.x] [PMID: 20412113]
[http://dx.doi.org/10.1016/S0140-6736(10)62307-0] [PMID: 21620466]
[PMID: 2810821]
[http://dx.doi.org/10.3748/wjg.v22.i44.9694] [PMID: 27956793]
[http://dx.doi.org/10.1097/PPO.0b013e3182756803] [PMID: 23187833]
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[http://dx.doi.org/10.1097/00006676-200011000-00003] [PMID: 11075987]
[http://dx.doi.org/10.1007/s10689-004-9549-8] [PMID: 15516847]
[http://dx.doi.org/10.2147/CEG.S289269] [PMID: 33603433]
[http://dx.doi.org/10.1007/978-3-030-53786-9_2]
[http://dx.doi.org/10.1016/S2468-1253(19)30347-4] [PMID: 31648972]
[http://dx.doi.org/10.1038/s41575-021-00457-x] [PMID: 34002083]
[http://dx.doi.org/10.1016/j.ejca.2018.07.005] [PMID: 30100160]
[http://dx.doi.org/10.25259/IJMS_92_2020]
[http://dx.doi.org/10.3748/wjg.v27.i27.4298] [PMID: 34366606]
[http://dx.doi.org/10.21037/jgo-20-118] [PMID: 34422401]
[http://dx.doi.org/10.3748/wjg.v24.i43.4846] [PMID: 30487695]
[http://dx.doi.org/10.1007/s10552-007-9002-z] [PMID: 17401636]
[http://dx.doi.org/10.1093/annonc/mdr541] [PMID: 22104574]
[http://dx.doi.org/10.3748/wjg.v20.i24.7830] [PMID: 24976721]
[http://dx.doi.org/10.21037/tgh.2019.06.02] [PMID: 31304427]
[http://dx.doi.org/10.1016/j.ccr.2005.04.023] [PMID: 15894267]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-1274] [PMID: 16299235]
[http://dx.doi.org/10.1007/s10038-005-0235-y] [PMID: 15824892]
[http://dx.doi.org/10.1111/pin.12114] [PMID: 24471965]
[http://dx.doi.org/10.1073/pnas.0601273103] [PMID: 16585505]
[http://dx.doi.org/10.1038/nm1087] [PMID: 15286780]
[http://dx.doi.org/10.1158/1078-0432.CCR-1121-3] [PMID: 15014009]
[http://dx.doi.org/10.2174/138945012800564103] [PMID: 22458520]
[http://dx.doi.org/10.1016/S0002-9440(10)64703-7] [PMID: 10623651]
[http://dx.doi.org/10.1593/neo.81618] [PMID: 19412434]
[http://dx.doi.org/10.1200/JCO.2006.07.8824] [PMID: 17235047]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2030] [PMID: 17283135]
[http://dx.doi.org/10.1016/j.cell.2009.11.007] [PMID: 19945376]
[http://dx.doi.org/10.1517/14728222.2011.645805] [PMID: 22239440]
[http://dx.doi.org/10.3389/fonc.2015.00023] [PMID: 25699241]
[http://dx.doi.org/10.3389/fonc.2014.00160] [PMID: 25009801]
[http://dx.doi.org/10.1016/j.febslet.2014.06.025] [PMID: 24937142]
[http://dx.doi.org/10.18632/oncotarget.240] [PMID: 21411864]
[http://dx.doi.org/10.1186/1479-5876-10-85] [PMID: 22554099]
[http://dx.doi.org/10.1016/j.ctrv.2003.07.007] [PMID: 15023437]
[http://dx.doi.org/10.1007/s11033-020-05435-1] [PMID: 32333246]
[http://dx.doi.org/10.3109/07853890.2014.912836] [PMID: 24897931]
[http://dx.doi.org/10.3389/fphys.2018.00335] [PMID: 29670543]
[http://dx.doi.org/10.1038/sj.onc.1209085] [PMID: 16288292]
[http://dx.doi.org/10.1002/jcb.25496] [PMID: 26774024]
[http://dx.doi.org/10.1038/nrc3500] [PMID: 23612460]
[http://dx.doi.org/10.1038/nri.2016.112] [PMID: 27885276]
[http://dx.doi.org/10.1093/abbs/gmy092] [PMID: 30165534]
[http://dx.doi.org/10.1016/j.canlet.2012.03.018] [PMID: 22445908]
[http://dx.doi.org/10.7554/eLife.33947] [PMID: 30074477]
[http://dx.doi.org/10.1053/j.gastro.2013.01.072] [PMID: 23622133]
[http://dx.doi.org/10.1016/j.semcancer.2018.08.007] [PMID: 30130664]
[http://dx.doi.org/10.4252/wjsc.v7.i3.547] [PMID: 25914762]
[http://dx.doi.org/10.1200/JCO.2008.16.6702] [PMID: 18539958]
[http://dx.doi.org/10.1016/j.stem.2007.06.002] [PMID: 18371365]
[http://dx.doi.org/10.1007/s40291-013-0024-9] [PMID: 23529353]
[http://dx.doi.org/10.1007/s13402-019-00448-w] [PMID: 31025257]
[http://dx.doi.org/10.1186/s12943-018-0797-x] [PMID: 29455658]
[http://dx.doi.org/10.3390/jcm10040566] [PMID: 33546207]
[http://dx.doi.org/10.1186/s40425-017-0257-y] [PMID: 28716061]
[http://dx.doi.org/10.1200/JCO.2019.37.4_suppl.TPS465]
[http://dx.doi.org/10.1159/000049159] [PMID: 11275700]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2411] [PMID: 28373362]
[http://dx.doi.org/10.1038/nature14169] [PMID: 25719666]
[http://dx.doi.org/10.1016/j.gene.2019.02.081] [PMID: 30898709]
[http://dx.doi.org/10.1200/JCO.2020.38.15_suppl.3581]
[http://dx.doi.org/10.1007/s10456-018-9645-2] [PMID: 30168025]
[http://dx.doi.org/10.1007/s11523-017-0518-1] [PMID: 28801849]
[http://dx.doi.org/10.1200/JCO.2008.20.0238] [PMID: 19307500]
[http://dx.doi.org/10.1007/s13402-020-00526-4] [PMID: 32504382]
[http://dx.doi.org/10.1158/1078-0432.CCR-20-1066] [PMID: 32943458]
[http://dx.doi.org/10.1200/jco.2016.34.4_suppl.196]
[http://dx.doi.org/10.1016/j.bbamcr.2006.11.001] [PMID: 17161475]
[http://dx.doi.org/10.1016/j.ccell.2020.03.013] [PMID: 32289276]
[http://dx.doi.org/10.1038/s41591-019-0368-8] [PMID: 30833752]
[http://dx.doi.org/10.1158/2159-8290.CD-17-1119] [PMID: 29247021]
[http://dx.doi.org/10.1038/nrc4000] [PMID: 26399658]
[http://dx.doi.org/10.1007/s40265-015-0477-8] [PMID: 26452567]
[http://dx.doi.org/10.1038/s41571-018-0105-0] [PMID: 30275515]
[http://dx.doi.org/10.1101/gad.1415606] [PMID: 16702400]
[http://dx.doi.org/10.21037/atm.2016.05.11] [PMID: 27275478]
[http://dx.doi.org/10.1111/j.1440-1746.2004.03487.x] [PMID: 15610448]
[http://dx.doi.org/10.1038/nrclinonc.2013.66] [PMID: 23629472]
[http://dx.doi.org/10.1016/j.jbior.2017.11.007] [PMID: 29221990]
[http://dx.doi.org/10.1155/2016/8962321] [PMID: 26941789]
[http://dx.doi.org/10.1097/MPA.0b013e3180333ae3] [PMID: 17446843]
[http://dx.doi.org/10.1038/s41571-018-0112-1] [PMID: 30341417]
[http://dx.doi.org/10.1097/MPA.0000000000001634] [PMID: 32833940]
[http://dx.doi.org/10.1196/annals.1414.024] [PMID: 18837898]
[http://dx.doi.org/10.1002/cam4.921] [PMID: 27671746]
[http://dx.doi.org/10.1038/s41575-018-0005-x] [PMID: 29717230]
[http://dx.doi.org/10.1080/08941939.2022.2129884] [PMID: 36191926]
[http://dx.doi.org/10.1097/COC.0000000000000278] [PMID: 26950464]
[http://dx.doi.org/10.1007/s10238-018-0540-3] [PMID: 30498929]
[http://dx.doi.org/10.1038/s41571-023-00746-1] [PMID: 36932224]
[http://dx.doi.org/10.1245/s10434-023-13281-1] [PMID: 36869916]
[http://dx.doi.org/10.1177/1756284819878660] [PMID: 31598136]
[http://dx.doi.org/10.1111/bph.12401] [PMID: 24024905]
[http://dx.doi.org/10.1016/j.critrevonc.2006.02.004] [PMID: 16725343]
[http://dx.doi.org/10.1016/j.clinthera.2017.08.015] [PMID: 28939405]
[http://dx.doi.org/10.1001/jamaoncol.2019.0684] [PMID: 31120501]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-4042] [PMID: 32156749]
[http://dx.doi.org/10.4251/wjgo.v12.i2.182] [PMID: 32104549]
[http://dx.doi.org/10.1093/jnci/dju413] [PMID: 25638248]
[http://dx.doi.org/10.1177/1758835919850367] [PMID: 31205510]
[http://dx.doi.org/10.1371/journal.pone.0206688] [PMID: 30412592]
[http://dx.doi.org/10.1016/S1470-2045(16)00172-8] [PMID: 27160474]
[http://dx.doi.org/10.3390/cancers11040484] [PMID: 30959763]
[http://dx.doi.org/10.1186/s12885-020-06945-8] [PMID: 32434547]
[http://dx.doi.org/10.1177/1758835919853196] [PMID: 31360237]
[http://dx.doi.org/10.1016/j.critrevonc.2017.03.025] [PMID: 28602164]
[http://dx.doi.org/10.1097/MD.0000000000006769] [PMID: 28489753]
[http://dx.doi.org/10.1159/000080993] [PMID: 15539911]
[http://dx.doi.org/10.22270/jddt.v7i3.1443]
[http://dx.doi.org/10.1002/ptr.5669] [PMID: 27384261]
[http://dx.doi.org/10.3390/nu8070433] [PMID: 27438851]
[http://dx.doi.org/10.1016/j.phytochem.2006.11.009] [PMID: 17184797]
[http://dx.doi.org/10.1016/j.uct.2006.10.001]
[http://dx.doi.org/10.2174/1574892813666181119123035] [PMID: 30451116]
[http://dx.doi.org/10.1002/jccs.201190005]
[http://dx.doi.org/10.3389/fnagi.2014.00245] [PMID: 25278877]
[http://dx.doi.org/10.1615/IntJMedMushr.v16.i1.20] [PMID: 24940901]
[http://dx.doi.org/10.1016/j.biotechadv.2018.02.002] [PMID: 29408560]
[http://dx.doi.org/10.1016/j.phytochem.2011.02.024] [PMID: 21429537]
[http://dx.doi.org/10.2174/1381612013397483] [PMID: 11472261]
[http://dx.doi.org/10.1517/13543784.17.4.583] [PMID: 18363522]
[http://dx.doi.org/10.1016/j.phrs.2009.01.017] [PMID: 19429468]
[http://dx.doi.org/10.12691/ajps-1-6-1]
[http://dx.doi.org/10.2174/0929867033457151] [PMID: 12871118]
[http://dx.doi.org/10.4161/cc.3.12.1278] [PMID: 15539947]
[http://dx.doi.org/10.1021/mp700113r] [PMID: 17999464]
[http://dx.doi.org/10.1002/ijc.31867] [PMID: 30226272]
[PMID: 20027668]
[PMID: 23116317]
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0174] [PMID: 17041101]
[http://dx.doi.org/10.1016/j.canlet.2013.08.002] [PMID: 23933177]
[http://dx.doi.org/10.1097/CAD.0b013e32832afc04] [PMID: 19384191]
[http://dx.doi.org/10.1016/j.canlet.2014.12.007] [PMID: 25497868]
[http://dx.doi.org/10.1186/1747-1028-3-14] [PMID: 18834508]
[http://dx.doi.org/10.3390/molecules20059183] [PMID: 26007179]
[http://dx.doi.org/10.1517/14796694.1.3.405] [PMID: 16556014]
[http://dx.doi.org/10.1007/978-0-387-46401-5_5] [PMID: 17569209]
[http://dx.doi.org/10.1002/tox.23103] [PMID: 33496383]
[http://dx.doi.org/10.1007/s40495-015-0018-x] [PMID: 26457241]
[http://dx.doi.org/10.3892/or.2015.4159] [PMID: 26238775]
[http://dx.doi.org/10.1111/1750-3841.13793] [PMID: 28771714]
[http://dx.doi.org/10.1002/jcb.24612] [PMID: 23794119]
[http://dx.doi.org/10.3109/07357900903287006] [PMID: 20121547]
[http://dx.doi.org/10.1016/j.canlet.2008.03.009] [PMID: 18479807]
[http://dx.doi.org/10.1080/01635580802416703] [PMID: 19003584]
[http://dx.doi.org/10.1038/s41598-017-10672-9] [PMID: 28855623]
[http://dx.doi.org/10.1208/s12248-015-9811-z] [PMID: 26335307]
[http://dx.doi.org/10.3797/scipharm.ISP.2015.10] [PMID: 27110509]
[http://dx.doi.org/10.1016/j.jcis.2010.05.022] [PMID: 20627257]
[http://dx.doi.org/10.1016/j.surg.2011.12.014] [PMID: 22284765]
[http://dx.doi.org/10.1002/cncr.21300] [PMID: 16092118]
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00644] [PMID: 26716471]
[http://dx.doi.org/10.1517/17425247.2014.916686] [PMID: 24857605]
[http://dx.doi.org/10.1002/mabi.201000084] [PMID: 20572274]
[http://dx.doi.org/10.1080/01635581.2017.1285405] [PMID: 28287321]
[http://dx.doi.org/10.1039/C1NR11271F] [PMID: 22080352]
[http://dx.doi.org/10.1158/1535-7163.MCT-12-1227] [PMID: 23704793]