Omega-3 Fatty Acid Treatment Combined with Chemotherapy to Prevent
Toxicity, Drug Resistance, and Metastasis in Cancer

Sneha       Soni; Meaghan       Torvund; Chandi    C.   Mandal
Abstract

Despite advances in treatment, individuals diagnosed with cancer are often at risk of suffering from metastasis, tumor recurrence, therapy resistance, and off-target toxicities from conventional chemo-, radio-, and endocrine- therapies. Drugs with potent anticancer and antimetastatic activity but with milder side effects can be combined with conventional therapies to increase efficacy, reduce therapy resistance, and decrease toxicity. Substantial data from epidemiological, cell culture, animal, and clinical studies have established the anticancer potential of nontoxic omega-3 fatty acids. This paper highlights the beneficial effects of omega-3 fatty acid treatment when used in combination with conventional therapies to protect against metastasis, enhance therapeutic efficacy, and prevent the off-target toxicity caused by conventional therapies. These omega-3 fatty acids target therapy-induced central players, NF-κB and ROS, to prevent drug-associated metastasis, therapy resistance, and off-target toxicities.
Keywords: Chemotherapy, omega-3 fatty acids, metastasis, therapy resistance, toxicity, NF-κB, ROS.
Graphical Abstract

[1] 
Nagai H, Kim YH. Cancer prevention from the perspective of global cancer burden patterns. J Thorac Dis  2017; 9(3): 448-51.
[http://dx.doi.org/10.21037/jtd.2017.02.75] [PMID: 28449441] 
[2] 
Nussbaumer S, Bonnabry P, Veuthey JL, Fleury-Souverain S. Analysis of anticancer drugs: a review. Talanta  2011; 85(5): 2265-89.
[http://dx.doi.org/10.1016/j.talanta.2011.08.034] [PMID: 21962644] 
[3] 
Camargo CQ, Brunetta HS, Nunes EA. Effects of cotreatment with omega-3 polyunsaturated fatty acids and anticancer agents on oxidative stress parameters: a systematic review of in vitro, animal, and human studies. Nutr Rev  2018; 76(10): 765-77.
[http://dx.doi.org/10.1093/nutrit/nuy029] [PMID: 30010957] 
[4] 
Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature  2019; 575(7782): 299-309.
[http://dx.doi.org/10.1038/s41586-019-1730-1] [PMID: 31723286] 
[5] 
Schirrmacher V. From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment (Review). Int J Oncol  2019; 54(2): 407-19.
[PMID: 30570109] 
[6] 
Steeg PS. Targeting metastasis. Nat Rev Cancer  2016; 16(4): 201-18.
[http://dx.doi.org/10.1038/nrc.2016.25] [PMID: 27009393] 
[7] 
Qian C-N, Mei Y, Zhang J. Cancer metastasis: issues and challenges. Chin J Cancer  2017; 36(1): 38-8.
[http://dx.doi.org/10.1186/s40880-017-0206-7] [PMID: 28372569] 
[8] 
Chakraborty S, Rahman T. The difficulties in cancer treatment. Ecancermedicalscience  2012; 6: ed16-6.
[PMID: 24883085] 
[9] 
Guan X. Cancer metastases: challenges and opportunities. Acta Pharm Sin B  2015; 5(5): 402-18.
[http://dx.doi.org/10.1016/j.apsb.2015.07.005] [PMID: 26579471] 
[10] 
Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther  2020; 5(1): 28-8.
[http://dx.doi.org/10.1038/s41392-020-0134-x] [PMID: 32296047] 
[11] 
Siddiqui RA, Harvey KA, Xu Z, Bammerlin EM, Walker C, Altenburg JD. Docosahexaenoic acid: a natural powerful adjuvant that improves efficacy for anticancer treatment with no adverse effects. Biofactors  2011; 37(6): 399-412.
[http://dx.doi.org/10.1002/biof.181] [PMID: 22038684] 
[12] 
Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos E. The challenge of drug resistance in cancer treatment: a current overview. Clin Exp Metastasis  2018; 35(4): 309-18.
[http://dx.doi.org/10.1007/s10585-018-9903-0] [PMID: 29799080] 
[13] 
Housman G, Byler S, Heerboth S, et al. Drug resistance in cancer: an overview. Cancers (Basel)  2014; 6(3): 1769-92.
[http://dx.doi.org/10.3390/cancers6031769] [PMID: 25198391] 
[14] 
Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull  2017; 7(3): 339-48.
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215] 
[15] 
Devlin EJ, Denson LA, Whitford HS. Cancer treatment side effects: a meta-analysis of the relationship between response expectancies and experience. J Pain Symptom Manage  2017; 54(2): 245-258.e2.
[http://dx.doi.org/10.1016/j.jpainsymman.2017.03.017] [PMID: 28533160] 
[16] 
de Sá Junior PL, Câmara DAD, Porcacchia AS, et al. The roles of ros in cancer heterogeneity and therapy. Oxid Med Cell Longev  2017; 2017: 2467940.
[http://dx.doi.org/10.1155/2017/2467940] [PMID: 29123614] 
[17] 
Merendino N, Costantini L, Manzi L, Molinari R, D’Eliseo D, Velotti F. Dietary ω -3 polyunsaturated fatty acid DHA: a potential adjuvant in the treatment of cancer. BioMed Res Int  2013; 2013: 310186.
[http://dx.doi.org/10.1155/2013/310186] [PMID: 23762838] 
[18] 
Zhang J, Lei W, Chen X, Wang S, Qian W. Oxidative stress response induced by chemotherapy in leukemia treatment. Mol Clin Oncol  2018; 8(3): 391-9.
[http://dx.doi.org/10.3892/mco.2018.1549] [PMID: 29599981] 
[19] 
Mariappan N, Elks CM, Sriramula S, et al. NF-kappaB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes. Cardiovasc Res  2010; 85(3): 473-83.
[http://dx.doi.org/10.1093/cvr/cvp305] [PMID: 19729361] 
[20] 
Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxidative stress and toxicity. J Toxicol  2012; 2012: 645460.
[http://dx.doi.org/10.1155/2012/645460] [PMID: 22919381] 
[21] 
Kim SJ, Kim HS, Seo YR. Understanding of ROS-inducing strategy in anticancer therapy. Oxid Med Cell Longev  2019; 2019: 5381692.
[http://dx.doi.org/10.1155/2019/5381692] [PMID: 31929855] 
[22] 
Conklin KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther  2004; 3(4): 294-300.
[http://dx.doi.org/10.1177/1534735404270335] [PMID: 15523100] 
[23] 
Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol  2012; 2012: 137289-9.
[http://dx.doi.org/10.5402/2012/137289] [PMID: 23119185] 
[24] 
Huang G, Pan ST. ROS-mediated therapeutic strategy in chemo-/radiotherapy of head and neck cancer. Oxid Med Cell Longev  2020; 2020: 5047987.
[http://dx.doi.org/10.1155/2020/5047987] [PMID: 32774675] 
[25] 
Yang H, Villani RM, Wang H, et al. The role of cellular reactive oxygen species in cancer chemotherapy. J Exp Clin Cancer Res  2018; 37(1): 266.
[http://dx.doi.org/10.1186/s13046-018-0909-x] [PMID: 30382874] 
[26] 
Kumar Rajendran N, George BP, Chandran R, Tynga IM, Houreld N, Abrahamse H. The influence of light on reactive oxygen species and NF-кB in disease progression. Antioxidants  2019; 8(12): 640.
[http://dx.doi.org/10.3390/antiox8120640] [PMID: 31842333] 
[27] 
Nakano H, Nakajima A, Sakon-Komazawa S, Piao JH, Xue X, Okumura K. Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ  2006; 13(5): 730-7.
[http://dx.doi.org/10.1038/sj.cdd.4401830] [PMID: 16341124] 
[28] 
Perkins ND, Gilmore TD. Good cop, bad cop: the different faces of NF-kappaB. Cell Death Differ  2006; 13(5): 759-72.
[http://dx.doi.org/10.1038/sj.cdd.4401838] [PMID: 16410803] 
[29] 
Roux C, Jafari SM, Shinde R, et al. Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1. Proc Natl Acad Sci USA  2019; 116(10): 4326-35.
[http://dx.doi.org/10.1073/pnas.1819473116] [PMID: 30770442] 
[30] 
Saini RK, Keum YS. Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance - A review. Life Sci  2018; 203: 255-67.
[http://dx.doi.org/10.1016/j.lfs.2018.04.049] [PMID: 29715470] 
[31] 
Freitas RDS, Campos MM. Protective effects of omega-3 fatty acids in cancer-related complications. Nutrients  2019; 11(5): E945.
[http://dx.doi.org/10.3390/nu11050945] [PMID: 31035457] 
[32] 
Markham M-J, Dog TL. 32 - Dietary Supplements and Hemostasis, in Consultative Hemostasis and Thrombosis (Third Edition).  Philadelphia: W.B. Saunders 2013; pp. 595-600.
[http://dx.doi.org/10.1016/B978-1-4557-2296-9.00032-4] 
[33] 
Sharma T, Mandal CC. Omega-3 fatty acids in pathological calcification and bone health. J Food Biochem  2020; 44(8): e13333.
[http://dx.doi.org/10.1111/jfbc.13333] [PMID: 32548903] 
[34] 
Moloudizargari M, Mortaz E, Asghari MH, Adcock IM, Redegeld FA, Garssen J. Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review. Oncotarget  2018; 9(14): 11858-75.
[http://dx.doi.org/10.18632/oncotarget.24405] [PMID: 29545942] 
[35] 
Gu Z, Shan K, Chen H, Chen YQ. n-3 polyunsaturated fatty acids and their role in cancer chemoprevention. Curr Pharmacol Rep  2015; 1(5): 283-94.
[http://dx.doi.org/10.1007/s40495-015-0043-9] [PMID: 26457243] 
[36] 
Nabavi SF, Bilotto S, Russo GL, et al. Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials. Cancer Metastasis Rev  2015; 34(3): 359-80.
[http://dx.doi.org/10.1007/s10555-015-9572-2] [PMID: 26227583] 
[37] 
Stephenson JA, Al-Taan O, Arshad A, Morgan B, Metcalfe MS, Dennison AR. The multifaceted effects of omega-3 polyunsaturated Fatty acids on the hallmarks of cancer. J Lipids  2013; 2013: 261247.
[http://dx.doi.org/10.1155/2013/261247] [PMID: 23762563] 
[38] 
D’Eliseo D, Velotti F. Omega-3 fatty acids and cancer cell cytotoxicity: implications for multi-targeted cancer therapy. J Clin Med  2016; 5(2): 15.
[http://dx.doi.org/10.3390/jcm5020015] [PMID: 26821053] 
[39] 
Ghosh-Choudhury T, Mandal CC, Woodruff K, et al. Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth. Breast Cancer Res Treat  2009; 118(1): 213-28.
[http://dx.doi.org/10.1007/s10549-008-0227-7] [PMID: 18953692] 
[40] 
Joshi AA, Hegde MV, Adekar SP. Omega-3 fatty acids in cancer: insight into the mechanism of actions in preclinical cancer models.  Springer 2016; pp. 157-71.
[http://dx.doi.org/10.1007/978-3-319-40458-5_12] 
[41] 
Yeung KT, Yang J. Epithelial-mesenchymal transition in tumor metastasis. Mol Oncol  2017; 11(1): 28-39.
[http://dx.doi.org/10.1002/1878-0261.12017] [PMID: 28085222] 
[42] 
Wang H, Unternaehrer JJ. Epithelial-mesenchymal Transition and cancer stem cells: at the crossroads of differentiation and dedifferentiation. Dev Dyn  2019; 248(1): 10-20.
[http://dx.doi.org/10.1002/dvdy.24678] [PMID: 30303578] 
[43] 
Wu Y, Zhou BP. Inflammation: a driving force speeds cancer metastasis. Cell Cycle  2009; 8(20): 3267-73.
[http://dx.doi.org/10.4161/cc.8.20.9699] [PMID: 19770594] 
[44] 
Zhang S, Yang X, Wang L, Zhang C. Interplay between inflammatory tumor microenvironment and cancer stem cells. Oncol Lett  2018; 16(1): 679-86.
[http://dx.doi.org/10.3892/ol.2018.8716] [PMID: 29963133] 
[45] 
Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res  2014; 2014: 149185.
[http://dx.doi.org/10.1155/2014/149185] [PMID: 24901008] 
[46] 
Maier HJ, Schmidt-Strassburger U, Huber MA, Wiedemann EM, Beug H, Wirth T. NF-kappaB promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells. Cancer Lett  2010; 295(2): 214-28.
[http://dx.doi.org/10.1016/j.canlet.2010.03.003] [PMID: 20350779] 
[47] 
Kumar M, Allison DF, Baranova NN, et al. NF-κB regulates mesenchymal transition for the induction of non-small cell lung cancer initiating cells. PLoS One  2013; 8(7): e68597.
[http://dx.doi.org/10.1371/journal.pone.0068597] [PMID: 23935876] 
[48] 
Qin X, Yan M, Wang X, et al. Cancer-associated fibroblast-derived IL-6 promotes head and neck cancer progression via the osteopontin-NF-kappa B signaling pathway. Theranostics  2018; 8(4): 921-40.
[http://dx.doi.org/10.7150/thno.22182] [PMID: 29463991] 
[49] 
Liu W, Wang H, Bai F, et al. IL-6 promotes metastasis of non-small-cell lung cancer by up-regulating TIM-4 via NF-κB. Cell Prolif  2020; 53(3): e12776.
[http://dx.doi.org/10.1111/cpr.12776] [PMID: 32020709] 
[50] 
Storci G, Sansone P, Mari S, et al. TNFalpha up-regulates SLUG via the NF-kappaB/HIF1alpha axis, which imparts breast cancer cells with a stem cell-like phenotype. J Cell Physiol  2010; 225(3): 682-91.
[http://dx.doi.org/10.1002/jcp.22264] [PMID: 20509143] 
[51] 
Mandal CC, Ghosh-Choudhury T, Yoneda T, Choudhury GG, Ghosh-Choudhury N. Fish oil prevents breast cancer cell metastasis to bone. Biochem Biophys Res Commun  2010; 402(4): 602-7.
[http://dx.doi.org/10.1016/j.bbrc.2010.10.063] [PMID: 20971068] 
[52] 
Rahman MM, Veigas JM, Williams PJ, Fernandes G. DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA. Breast Cancer Res Treat  2013; 141(3): 341-52.
[http://dx.doi.org/10.1007/s10549-013-2703-y] [PMID: 24062211] 
[53] 
Mandal CC, Ghosh-Choudhury T, Dey N, Choudhury GG, Ghosh-Choudhury N. miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression. Carcinogenesis  2012; 33(10): 1897-908.
[http://dx.doi.org/10.1093/carcin/bgs198] [PMID: 22678116] 
[54] 
Yun EJ, Song KS, Shin S, et al. Docosahexaenoic acid suppresses breast cancer cell metastasis by targeting matrix-metalloproteinases. Oncotarget  2016; 7(31): 49961-71.
[http://dx.doi.org/10.18632/oncotarget.10266] [PMID: 27363023] 
[55] 
Sharma T, Sharma A, Maheshwari R, Pachori G, Kumari P, Mandal CC. Docosahexaenoic Acid (DHA) inhibits bone morphogenetic protein-2 (BMP-2) elevated osteoblast potential of metastatic breast cancer (MDA-MB-231) cells in mammary microcalcification. Nutr Cancer  2020; 72(5): 873-83.
[http://dx.doi.org/10.1080/01635581.2019.1651879] [PMID: 31409173] 
[56] 
Awolaran O, Brooks SA, Lavender V. Breast cancer osteomimicry and its role in bone specific metastasis; an integrative, systematic review of preclinical evidence. Breast  2016; 30: 156-71.
[http://dx.doi.org/10.1016/j.breast.2016.09.017] [PMID: 27750106] 
[57] 
Davison Z, Nicholson RI, Hiscox S, Heard CM. Co-administration of fish oil with signal transduction inhibitors has anti-migration effects in breast cancer cell lines, in vitro. Open Biochem J  2018; 12: 130-48.
[http://dx.doi.org/10.2174/1874091X01812010130] [PMID: 30288178] 
[58] 
Chen Z, Zhang Y, Jia C, et al. mTORC1/2 targeted by n-3 polyunsaturated fatty acids in the prevention of mammary tumorigenesis and tumor progression. Oncogene  2014; 33(37): 4548-57.
[http://dx.doi.org/10.1038/onc.2013.402] [PMID: 24096482] 
[59] 
Li CC, Yao HT, Cheng FJ, et al. Docosahexaenoic acid downregulates EGF-induced urokinase plasminogen activator and matrix metalloproteinase 9 expression by inactivating EGFR/ErbB2 signaling in SK-BR3 breast cancer cells. Nutr Cancer  2015; 67(5): 771-82.
[http://dx.doi.org/10.1080/01635581.2015.1037961] [PMID: 25970488] 
[60] 
Dimri M, Bommi PV, Sahasrabuddhe AA, Khandekar JD, Dimri GP. Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells. Carcinogenesis  2010; 31(3): 489-95.
[http://dx.doi.org/10.1093/carcin/bgp305] [PMID: 19969553] 
[61] 
Altenburg JD, Siddiqui RA. Omega-3 polyunsaturated fatty acids down-modulate CXCR4 expression and function in MDA-MB-231 breast cancer cells. Mol Cancer Res  2009; 7(7): 1013-20.
[http://dx.doi.org/10.1158/1541-7786.MCR-08-0385] [PMID: 19567784] 
[62] 
Chen HW, Chao CY, Lin LL, et al. Inhibition of matrix metalloproteinase-9 expression by docosahexaenoic acid mediated by heme oxygenase 1 in 12-O-tetradecanoylphorbol-13-acetate-induced MCF-7 human breast cancer cells. Arch Toxicol  2013; 87(5): 857-69.
[http://dx.doi.org/10.1007/s00204-012-1003-3] [PMID: 23288142] 
[63] 
Wang SC, Sun HL, Hsu YH, et al. α-Linolenic acid inhibits the migration of human triple-negative breast cancer cells by attenuating Twist1 expression and suppressing Twist1-mediated epithelial-mesenchymal transition. Biochem Pharmacol  2020; 180: 114152.
[http://dx.doi.org/10.1016/j.bcp.2020.114152] [PMID: 32679125] 
[64] 
Sung NJ, Kim NH, Bae NY, Jo HS, Park SA. DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells. Biosci Rep  2020; 40(3): BSR20200164.
[http://dx.doi.org/10.1042/BSR20200164] [PMID: 32141512] 
[65] 
Yi L, Zhang QY, Mi MT. Role of Rho GTPase in inhibiting metastatic ability of human prostate cancer cell line PC-3 by omega-3 polyunsaturated fatty acid. Ai Zheng  2007; 26(12): 1281-6.
[66] 
Nakajima T, Kubota N, Tsutsumi T, et al. Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells. Br J Pharmacol  2009; 156(3): 420-31.
[http://dx.doi.org/10.1111/j.1476-5381.2008.00059.x] [PMID: 19154441] 
[67] 
Wu Z, Chen CY, Kao CL, Jiang Y, Liu CM. Docosahexaenoic acid inhibits lipopolysaccharide-induced metastatic activities by decreasing inflammation on prostate cancer cell. Pharmazie  2019; 74(11): 675-9.
[PMID: 31739836] 
[68] 
Bai X, Shao J, Zhou S, et al. Inhibition of lung cancer growth and metastasis by DHA and its metabolite, RvD1, through miR-138-5p/FOXC1 pathway. J Exp Clin Cancer Res  2019; 38(1): 479.
[http://dx.doi.org/10.1186/s13046-019-1478-3] [PMID: 31783879] 
[69] 
Yin Y, Sui C, Meng F, Ma P, Jiang Y. The omega-3 polyunsaturated fatty acid docosahexaenoic acid inhibits proliferation and progression of non-small cell lung cancer cells through the reactive oxygen species-mediated inactivation of the PI3K /Akt pathway. Lipids Health Dis  2017; 16(1): 87.
[http://dx.doi.org/10.1186/s12944-017-0474-x] [PMID: 28468627] 
[70] 
Zu Y, Hu Y, Yu X, Jiang S. Docetaxel-loaded bovine serum albumin nanoparticles conjugated docosahexaenoic acid for inhibiting lung cancer metastasis to bone. Anticancer Agents Med Chem  2017; 17(4): 542-51.
[http://dx.doi.org/10.2174/1871520616666160817143656] [PMID: 27539313] 
[71] 
D’Eliseo D, Di Rocco G, Loria R, Soddu S, Santoni A, Velotti F. Epitelial-to-mesenchimal transition and invasion are upmodulated by tumor-expressed granzyme B and inhibited by docosahexaenoic acid in human colorectal cancer cells. J Exp Clin Cancer Res  2016; 35: 24.
[http://dx.doi.org/10.1186/s13046-016-0302-6] [PMID: 26830472] 
[72] 
Wang YC, Wu YN, Wang SL, et al. Docosahexaenoic acid modulates invasion and metastasis of human ovarian cancer via multiple molecular pathways. Int J Gynecol Cancer  2016; 26(6): 994-1003.
[http://dx.doi.org/10.1097/IGC.0000000000000746] [PMID: 27258728] 
[73] 
Lin CR, Chu TM, Luo A, et al. Omega-3 polyunsaturated fatty acids suppress metastatic features of human cholangiocarcinoma cells by suppressing twist. J Nutr Biochem  2019; 74: 108245.
[http://dx.doi.org/10.1016/j.jnutbio.2019.108245] [PMID: 31678746] 
[74] 
Rahman MM, Bhattacharya A, Fernandes G. Docosahexaenoic acid is more potent inhibitor of osteoclast differentiation in RAW 264.7 cells than eicosapentaenoic acid. J Cell Physiol  2008; 214(1): 201-9.
[http://dx.doi.org/10.1002/jcp.21188] [PMID: 17929247] 
[75] 
Yuan J, Akiyama M, Nakahama K, Sato T, Uematsu H, Morita I. The effects of polyunsaturated fatty acids and their metabolites on osteoclastogenesis in vitro. Prostaglandins Other Lipid Mediat  2010; 92(1-4): 85-90.
[http://dx.doi.org/10.1016/j.prostaglandins.2010.04.001] [PMID: 20394833] 
[76] 
Khadge S, Thiele GM, Sharp JG, et al. Long-chain omega-3 polyunsaturated fatty acids decrease mammary tumor growth, multiorgan metastasis and enhance survival. Clin Exp Metastasis  2018; 35(8): 797-818.
[http://dx.doi.org/10.1007/s10585-018-9941-7] [PMID: 30327985] 
[77] 
Jiang T, Chen L, Huang Y, et al. Metformin and docosahexaenoic acid hybrid micelles for premetastatic niche modulation and tumor metastasis suppression. Nano Lett  2019; 19(6): 3548-62.
[http://dx.doi.org/10.1021/acs.nanolett.9b00495] [PMID: 31026397] 
[78] 
Vara-Messler M, Pasqualini ME, Comba A, et al. Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis. Eur J Nutr  2017; 56(2): 509-19.
[http://dx.doi.org/10.1007/s00394-015-1096-6] [PMID: 26582578] 
[79] 
Kansal S, Bhatnagar A, Agnihotri N. Fish oil suppresses cell growth and metastatic potential by regulating PTEN and NF-κB signaling in colorectal cancer. PLoS One  2014; 9(1): e84627-7.
[http://dx.doi.org/10.1371/journal.pone.0084627] [PMID: 24416253] 
[80] 
Ichihara H, Zako K, Komizu Y, Goto K, Ueoka R. Therapeutic effects of hybrid liposomes composed of phosphatidylcholine and docosahexaenoic acid on the hepatic metastasis of colon carcinoma along with apoptosis in vivo. Biol Pharm Bull  2011; 34(6): 901-5.
[http://dx.doi.org/10.1248/bpb.34.901] [PMID: 21628892] 
[81] 
Hawcroft G, Volpato M, Marston G, et al. The omega-3 polyunsaturated fatty acid eicosapentaenoic acid inhibits mouse MC-26 colorectal cancer cell liver metastasis via inhibition of PGE2-dependent cell motility. Br J Pharmacol  2012; 166(5): 1724-37.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01882.x] [PMID: 22300262] 
[82] 
Zou S, Meng X, Meng Y, et al. Microarray analysis of anti-cancer effects of docosahexaenoic acid on human colon cancer model in nude mice. Int J Clin Exp Med  2015; 8(4): 5075-84.
[PMID: 26131080] 
[83] 
Darwito D, Dharmana E, Riwanto I, et al. Effects of omega-3 supplementation on Ki-67 and VEGF expression levels and clinical outcomes of locally advanced breast cancer patients treated with neoadjuvant CAF chemotherapy: a randomized controlled trial report. Asian Pac J Cancer Prev  2019; 20(3): 911-6.
[http://dx.doi.org/10.31557/APJCP.2019.20.3.911] [PMID: 30912414] 
[84] 
Arshad A, Isherwood J, Mann C, et al. Intravenous ω-3 fatty acids plus gemcitabine. JPEN J Parenter Enteral Nutr  2017; 41(3): 398-403.
[http://dx.doi.org/10.1177/0148607115595221] [PMID: 26220200] 
[85] 
Arshad A, Chung WY, Steward W, Metcalfe MS, Dennison AR. Reduction in circulating pro-angiogenic and pro-inflammatory factors is related to improved outcomes in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega-3 fish oil. HPB (Oxford)  2013; 15(6): 428-32.
[http://dx.doi.org/10.1111/hpb.12002] [PMID: 23458624] 
[86] 
Park M, Kim H. Anti-cancer mechanism of docosahexaenoic acid in pancreatic carcinogenesis: a mini-review. J Cancer Prev  2017; 22(1): 1-5.
[http://dx.doi.org/10.15430/JCP.2017.22.1.1] [PMID: 28382280] 
[87] 
Notarnicola M, Lorusso D, Tutino V, et al. Differential tissue fatty acids profiling between colorectal cancer patients with and without synchronous metastasis. Int J Mol Sci  2018; 19(4): E962.
[http://dx.doi.org/10.3390/ijms19040962] [PMID: 29570667] 
[88] 
Wang S, Xie J, Li H, Yang K. Differences of polyunsaturated fatty acid in patients with colorectal cancer and healthy people. J Cancer Res Ther  2015; 11(2): 459-63.
[http://dx.doi.org/10.4103/0973-1482.147702] [PMID: 26148618] 
[89] 
Qian BZ, Li J, Zhang H, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature  2011; 475(7355): 222-5.
[http://dx.doi.org/10.1038/nature10138] [PMID: 21654748] 
[90] 
Volpato M, Perry SL, Marston G, et al. Changes in plasma chemokine C-C motif ligand 2 levels during treatment with eicosapentaenoic acid predict outcome in patients undergoing surgery for colorectal cancer liver metastasis. Oncotarget  2016; 7(19): 28139-50.
[http://dx.doi.org/10.18632/oncotarget.8579] [PMID: 27058904] 
[91] 
Hull MA, Sprange K, Hepburn T, et al. Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial. Lancet  2018; 392(10164): 2583-94.
[http://dx.doi.org/10.1016/S0140-6736(18)31775-6] [PMID: 30466866] 
[92] 
Pires BR, Mencalha AL, Ferreira GM, et al. NF-kappaB Is Involved in the Regulation of EMT Genes in Breast Cancer Cells. PLoS One  2017; 12(1): e0169622.
[http://dx.doi.org/10.1371/journal.pone.0169622] [PMID: 28107418] 
[93] 
Neil JR, Schiemann WP. Altered TAB1:I kappaB kinase interaction promotes transforming growth factor beta-mediated nuclear factor-kappaB activation during breast cancer progression. Cancer Res  2008; 68(5): 1462-70.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-3094] [PMID: 18316610] 
[94] 
Pantuck AJ, An J, Liu H, Rettig MB. NF-kappaB-dependent plasticity of the epithelial to mesenchymal transition induced by Von Hippel-Lindau inactivation in renal cell carcinomas. Cancer Res  2010; 70(2): 752-61.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2211] [PMID: 20068166] 
[95] 
Yan M, Xu Q, Zhang P, Zhou XJ, Zhang ZY, Chen WT. Correlation of NF-kappaB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma. BMC Cancer  2010; 10: 437-7.
[http://dx.doi.org/10.1186/1471-2407-10-437] [PMID: 20716363] 
[96] 
Vyas D, Lopez-Hisijos N, Shah P, et al. A second-generation proteasome inhibitor and doxorubicin modulates IL-6, pSTAT-3 and NF-kB activity in mda-mb-231 breast cancer cells. J Nanosci Nanotechnol  2017; 17(1): 175-85.
[http://dx.doi.org/10.1166/jnn.2017.12427] [PMID: 29617099] 
[97] 
Tian ZC, Wang JQ, Ge H. Apatinib ameliorates doxorubicin-induced migration and cancer stemness of osteosarcoma cells by inhibiting Sox2 via STAT3 signalling. J Orthop Translat  2019; 22: 132-41.
[http://dx.doi.org/10.1016/j.jot.2019.07.003] [PMID: 32440509] 
[98] 
Latifi A, Abubaker K, Castrechini N, et al. Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile. J Cell Biochem  2011; 112(10): 2850-64.
[http://dx.doi.org/10.1002/jcb.23199] [PMID: 21618587] 
[99] 
Karagiannis GS, Condeelis JS, Oktay MH. Chemotherapy-induced metastasis: molecular mechanisms, clinical manifestations, therapeutic interventions. Cancer Res  2019; 79(18): 4567-76.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-1147] [PMID: 31431464] 
[100] 
Volk-Draper L, Hall K, Griggs C, et al. Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner. Cancer Res  2014; 74(19): 5421-34.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0067] [PMID: 25274031] 
[101] 
Cho YH, Ro EJ, Yoon JS, et al. 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nat Commun  2020; 11(1): 5321.
[http://dx.doi.org/10.1038/s41467-020-19173-2] [PMID: 33087710] 
[102] 
Hardman WE. Omega-3 fatty acids to augment cancer therapy. J Nutr  2002; 132(11)(Suppl.): 3508S-12S.
[http://dx.doi.org/10.1093/jn/132.11.3508S] [PMID: 12421878] 
[103] 
Pritchard JR, Bruno PM, Gilbert LA, Capron KL, Lauffenburger DA, Hemann MT. Defining principles of combination drug mechanisms of action. Proc Natl Acad Sci USA  2013; 110(2): E170-9.
[http://dx.doi.org/10.1073/pnas.1210419110] [PMID: 23251029] 
[104] 
Arruebo M, Vilaboa N, Sáez-Gutierrez B, et al. Assessment of the evolution of cancer treatment therapies. Cancers (Basel)  2011; 3(3): 3279-330.
[http://dx.doi.org/10.3390/cancers3033279] [PMID: 24212956] 
[105] 
Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol  2005; 205(2): 275-92.
[http://dx.doi.org/10.1002/path.1706] [PMID: 15641020] 
[106] 
Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer  2013; 13(10): 714-26.
[http://dx.doi.org/10.1038/nrc3599] [PMID: 24060863] 
[107] 
Damen MPF, van Rheenen J, Scheele CLGJ. Targeting dormant tumor cells to prevent cancer recurrence. FEBS J  2021; 288(21): 6286-303.
[http://dx.doi.org/10.1111/febs.15626] [PMID: 33190412] 
[108] 
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell  2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230] 
[109] 
Bayat Mokhtari R, Homayouni TS, Baluch N, et al. Combination therapy in combating cancer. Oncotarget  2017; 8(23): 38022-43.
[http://dx.doi.org/10.18632/oncotarget.16723] [PMID: 28410237] 
[110] 
Shao Y, Pardini L, Pardini RS. Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1. Lipids  1995; 30(11): 1035-45.
[http://dx.doi.org/10.1007/BF02536289] [PMID: 8569432] 
[111] 
Hardman WE, Moyer MP, Cameron IL. Dietary fish oil sensitizes A549 lung xenografts to doxorubicin chemotherapy. Cancer Lett  2000; 151(2): 145-51.
[http://dx.doi.org/10.1016/S0304-3835(99)00396-1] [PMID: 10738108] 
[112] 
Mackie SJ, Sharma DM, Cooper AJ, Harris NM, Lwaleed BA. Meglumine Eicosapentaenoic acid (MeEPA) a new soluble omega-3 fatty acid formulation: in vitro bladder cancer cytotoxicity tests in combination with epirubicin and mitomycin. Prostaglandins Leukot Essent Fatty Acids  2006; 75(6): 367-73.
[http://dx.doi.org/10.1016/j.plefa.2006.07.002] [PMID: 16930970] 
[113] 
Cha MC, Meckling KA, Stewart C. Dietary docosahexaenoic acid levels influence the outcome of arabinosylcytosine chemotherapy in L1210 leukemic mice. Nutr Cancer  2002; 44(2): 176-81.
[http://dx.doi.org/10.1207/S15327914NC4402_09] [PMID: 12734065] 
[114] 
DeGraffenried LA, Friedrichs WE, Fulcher L, et al. Eicosapentaenoic acid restores tamoxifen sensitivity in breast cancer cells with high Akt activity. Ann Oncol  2003; 14(7): 1051-6.
[http://dx.doi.org/10.1093/annonc/mdg291] [PMID: 12853346] 
[115] 
Hardman WE, Moyer MP, Cameron IL. Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects. Br J Cancer  1999; 81(3): 440-8.
[http://dx.doi.org/10.1038/sj.bjc.6690713] [PMID: 10507768] 
[116] 
Rani I, Sharma B, Kumar S, Kaur S, Agnihotri N. Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma. Tumour Biol  2017; 39(3): 1010428317695019.
[http://dx.doi.org/10.1177/1010428317695019] [PMID: 28349837] 
[117] 
Corsetto PA, Colombo I, Kopecka J, Rizzo AM, Riganti C. ω-3 long chain polyunsaturated fatty acids as sensitizing agents and multidrug resistance revertants in cancer therapy. Int J Mol Sci  2017; 18(12): 2770.
[http://dx.doi.org/10.3390/ijms18122770] [PMID: 29261109] 
[118] 
Colas S, Paon L, Denis F, et al. Enhanced radiosensitivity of rat autochthonous mammary tumors by dietary docosahexaenoic acid. Int J Cancer  2004; 109(3): 449-54.
[http://dx.doi.org/10.1002/ijc.11725] [PMID: 14961586] 
[119] 
Cai F, Sorg O, Granci V, et al. Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines. Clin Nutr  2014; 33(1): 164-70.
[http://dx.doi.org/10.1016/j.clnu.2013.04.005] [PMID: 23672803] 
[120] 
Davis MP, Panikkar R. Sarcopenia associated with chemotherapy and targeted agents for cancer therapy. Ann Palliat Med  2019; 8(1): 86-101.
[http://dx.doi.org/10.21037/apm.2018.08.02] [PMID: 30525762] 
[121] 
Zhu S, Feng N, Lin G, et al. Metabolic Shift Induced by ω -3 PUFAs and Rapamycin Lead to Cancer Cell Death. Cell Physiol Biochem  2018; 48(6): 2318-36.
[http://dx.doi.org/10.1159/000492648] [PMID: 30114709] 
[122] 
Newell M, Brun M, Field CJ. Treatment with DHA modifies the response of MDA-MB-231 breast cancer cells and tumors from nu/nu mice to doxorubicin through apoptosis and cell cycle arrest. J Nutr  2019; 149(1): 46-56.
[http://dx.doi.org/10.1093/jn/nxy224] [PMID: 30601995] 
[123] 
Liu QY, Tan BK. Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines. Life Sci  2000; 67(10): 1207-18.
[http://dx.doi.org/10.1016/S0024-3205(00)00714-1] [PMID: 10954054] 
[124] 
Fahrmann JF, Hardman WE. Omega 3 fatty acids increase the chemo-sensitivity of B-CLL-derived cell lines EHEB and MEC-2 and of B-PLL-derived cell line JVM-2 to anti-cancer drugs doxorubicin, vincristine and fludarabine. Lipids Health Dis  2013; 12: 36-6.
[http://dx.doi.org/10.1186/1476-511X-12-36] [PMID: 23497075] 
[125] 
Fahrmann JF, Ballester OF, Ballester G, et al. Inhibition of nuclear factor kappa B activation in early-stage chronic lymphocytic leukemia by omega-3 fatty acids. Cancer Invest  2013; 31(1): 24-38.
[http://dx.doi.org/10.3109/07357907.2012.743553] [PMID: 23193970] 
[126] 
Shaikh SR. Biophysical and biochemical mechanisms by which dietary N-3 polyunsaturated fatty acids from fish oil disrupt membrane lipid rafts. J Nutr Biochem  2012; 23(2): 101-5.
[http://dx.doi.org/10.1016/j.jnutbio.2011.07.001] [PMID: 22137258] 
[127] 
Gelsomino G, Corsetto PA, Campia I, et al. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition. Mol Cancer  2013; 12: 137.
[http://dx.doi.org/10.1186/1476-4598-12-137] [PMID: 24225025] 
[128] 
Colas S, Mahéo K, Denis F, et al. Sensitization by dietary docosahexaenoic acid of rat mammary carcinoma to anthracycline: a role for tumor vascularization. Clin Cancer Res  2006; 12(19): 5879-86.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-0386] [PMID: 17020996] 
[129] 
Wynter MP, Russell ST, Tisdale MJ. Effect of n-3 fatty acids on the antitumour effects of cytotoxic drugs. In Vivo 2004; 18(5): 543-7.
[PMID: 15523890] 
[130] 
Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol  2011; 12(5): 489-95.
[http://dx.doi.org/10.1016/S1470-2045(10)70218-7] [PMID: 21296615] 
[131] 
Pastore CA, Orlandi SP, Gonzalez MC. Introduction of an omega-3 enriched oral supplementation for cancer patients close to the first chemotherapy: may it be a factor for poor compliance? Nutr Cancer  2014; 66(8): 1285-92.
[http://dx.doi.org/10.1080/01635581.2014.956253] [PMID: 25329228] 
[132] 
Blondy S, David V, Verdier M, Mathonnet M, Perraud A, Christou N. 5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes. Cancer Sci  2020; 111(9): 3142-54.
[http://dx.doi.org/10.1111/cas.14532] [PMID: 32536012] 
[133] 
Vasudevan A, Yu Y, Banerjee S, et al. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer. Cancer Prev Res (Phila)  2014; 7(11): 1138-48.
[http://dx.doi.org/10.1158/1940-6207.CAPR-14-0177] [PMID: 25193342] 
[134] 
Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le Floch O. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer  2009; 101(12): 1978-85.
[http://dx.doi.org/10.1038/sj.bjc.6605441] [PMID: 19920822] 
[135] 
Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer  2011; 117(16): 3774-80.
[http://dx.doi.org/10.1002/cncr.25933] [PMID: 21328326] 
[136] 
de Aguiar Pastore Silva J, Emilia de Souza Fabre M, Waitzberg DL. Omega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review. Clin Nutr  2015; 34(3): 359-66.
[http://dx.doi.org/10.1016/j.clnu.2014.11.005] [PMID: 25907586] 
[137] 
Braun T, Carvalho G, Fabre C, Grosjean J, Fenaux P, Kroemer G. Targeting NF-kappaB in hematologic malignancies. Cell Death Differ  2006; 13(5): 748-58.
[http://dx.doi.org/10.1038/sj.cdd.4401874] [PMID: 16498458] 
[138] 
Calviello G, Di Nicuolo F, Serini S, et al. Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil. Cancer Chemother Pharmacol  2005; 55(1): 12-20.
[http://dx.doi.org/10.1007/s00280-004-0846-6] [PMID: 15365767] 
[139] 
Granci V, Cai F, Lecumberri E, Clerc A, Dupertuis YM, Pichard C. Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway. Br J Nutr  2013; 109(7): 1188-95.
[http://dx.doi.org/10.1017/S000711451200308X] [PMID: 22874769] 
[140] 
Kuan CY, Walker TH, Luo PG, Chen CF. Long-chain polyunsaturated fatty acids promote paclitaxel cytotoxicity via inhibition of the MDR1 gene in the human colon cancer Caco-2 cell line. J Am Coll Nutr  2011; 30(4): 265-73.
[http://dx.doi.org/10.1080/07315724.2011.10719969] [PMID: 21917707] 
[141] 
Shaikh IA, Brown I, Schofield AC, Wahle KW, Heys SD. Docosahexaenoic acid enhances the efficacy of docetaxel in prostate cancer cells by modulation of apoptosis: the role of genes associated with the NF-kappaB pathway. Prostate  2008; 68(15): 1635-46.
[http://dx.doi.org/10.1002/pros.20830] [PMID: 18668525] 
[142] 
Li F, Sethi G. Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta  2010; 1805(2): 167-80.
[PMID: 20079806] 
[143] 
Xia Y, Shen S, Verma IM. NF-κB, an active player in human cancers. Cancer Immunol Res  2014; 2(9): 823-30.
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0112] [PMID: 25187272] 
[144] 
Khongthong P, Roseweir AK, Edwards J. The NF-KB pathway and endocrine therapy resistance in breast cancer. Endocr Relat Cancer  2019; 26(6): R369-80.
[http://dx.doi.org/10.1530/ERC-19-0087] [PMID: 32013374] 
[145] 
Bentires-Alj M, Barbu V, Fillet M, et al. NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells. Oncogene  2003; 22(1): 90-7.
[http://dx.doi.org/10.1038/sj.onc.1206056] [PMID: 12527911] 
[146] 
Jiang X, Chen C, Gu S, Zhang Z. Regulation of ABCG2 by nuclear factor kappa B affects the sensitivity of human lung adenocarcinoma A549 cells to arsenic trioxide. Environ Toxicol Pharmacol  2018; 57: 141-50.
[http://dx.doi.org/10.1016/j.etap.2017.12.011] [PMID: 29274627] 
[147] 
Zhang P, Chen X-B, Ding B-Q, Liu H-L, He T, et al. Down-regulation of ABCE1 inhibits temozolomide resistance in glioma through the PI3K/Akt/NF-κB signaling pathway. Biosci Rep  2018; 38(6)
[http://dx.doi.org/10.1042/BSR20181711] 
[148] 
Liu T, Wei R, Zhang Y, Chen W, Liu H. Association between NF-κB expression and drug resistance of liver cancer. Oncol Lett  2019; 17(1): 1030-4.
[PMID: 30655862] 
[149] 
Velaei K, Samadi N, Soltani S, Barazvan B, Soleimani Rad J. NFκBP65 transcription factor modulates resistance to doxorubicin through ABC transporters in breast cancer. Breast Cancer  2017; 24(4): 552-61.
[http://dx.doi.org/10.1007/s12282-016-0738-8] [PMID: 27878697] 
[150] 
Kim HG, Hien TT, Han EH, et al. Metformin inhibits P-glycoprotein expression via the NF-κB pathway and CRE transcriptional activity through AMPK activation. Br J Pharmacol  2011; 162(5): 1096-108.
[http://dx.doi.org/10.1111/j.1476-5381.2010.01101.x] [PMID: 21054339] 
[151] 
Aggarwal BB, Sung B. NF-κB in cancer: a matter of life and death. Cancer Discov  2011; 1(6): 469-71.
[http://dx.doi.org/10.1158/2159-8290.CD-11-0260] [PMID: 22586649] 
[152] 
Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell  2004; 6(3): 203-8.
[http://dx.doi.org/10.1016/j.ccr.2004.09.003] [PMID: 15380510] 
[153] 
Bauer JA, Lupica JA, Schmidt H, et al. Nitrosylcobalamin potentiates the anti-neoplastic effects of chemotherapeutic agents via suppression of survival signaling. PLoS One  2007; 2(12): e1313-3.
[http://dx.doi.org/10.1371/journal.pone.0001313] [PMID: 18074035] 
[154] 
Arlt A, Gehrz A, Müerköster S, et al. Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene  2003; 22(21): 3243-51.
[http://dx.doi.org/10.1038/sj.onc.1206390] [PMID: 12761494] 
[155] 
Esparza-López J, Medina-Franco H, Escobar-Arriaga E, León-Rodríguez E, Zentella-Dehesa A, Ibarra-Sánchez MJ. Doxorubicin induces atypical NF-κB activation through c-Abl kinase activity in breast cancer cells. J Cancer Res Clin Oncol  2013; 139(10): 1625-35.
[http://dx.doi.org/10.1007/s00432-013-1476-3] [PMID: 23892407] 
[156] 
Aggarwal BB, Shishodia S, Takada Y, et al. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res  2005; 11(20): 7490-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-1192] [PMID: 16243823] 
[157] 
Slagsvold JE, Pettersen CH, Størvold GL, Follestad T, Krokan HE, Schønberg SA. DHA alters expression of target proteins of cancer therapy in chemotherapy resistant SW620 colon cancer cells. Nutr Cancer  2010; 62(5): 611-21.
[http://dx.doi.org/10.1080/01635580903532366] [PMID: 20574922] 
[158] 
Park M, Lim JW, Kim H. Docoxahexaenoic acid induces apoptosis of pancreatic cancer cells by suppressing activation of STAT3 and NF-κB. Nutrients  2018; 10(11): E1621.
[http://dx.doi.org/10.3390/nu10111621] [PMID: 30400136] 
[159] 
Dantzer R, Meagher MW, Cleeland CS. Translational approaches to treatment-induced symptoms in cancer patients. Nat Rev Clin Oncol  2012; 9(7): 414-26.
[http://dx.doi.org/10.1038/nrclinonc.2012.88] [PMID: 22641361] 
[160] 
Remesh A. Toxicities of anticancer drugs and its management. 2012.
[http://dx.doi.org/10.5455/2319-2003.ijbcp000812] 
[161] 
Cleeland CS, Allen JD, Roberts SA, et al. Reducing the toxicity of cancer therapy: recognizing needs, taking action. Nat Rev Clin Oncol  2012; 9(8): 471-8.
[http://dx.doi.org/10.1038/nrclinonc.2012.99] [PMID: 22751283] 
[162] 
Hall S, Rudrawar S, Zunk M, et al. Protection against Radiotherapy-Induced Toxicity. Antioxidants  2016; 5(3): 22.
[http://dx.doi.org/10.3390/antiox5030022] [PMID: 27399787] 
[163] 
Zhang Y, Zhang B, Dong L, Chang P. Potential of omega-3 polyunsaturated fatty acids in managing chemotherapy- or radiotherapy-related intestinal microbial dysbiosis. Adv Nutr  2019; 10(1): 133-47.
[http://dx.doi.org/10.1093/advances/nmy076] [PMID: 30566596] 
[164] 
Ewaschuk JB, Almasud A, Mazurak VC. Role of n-3 fatty acids in muscle loss and myosteatosis. Appl Physiol Nutr Metab  2014; 39(6): 654-62.
[http://dx.doi.org/10.1139/apnm-2013-0423] [PMID: 24869970] 
[165] 
Shirai Y, Okugawa Y, Hishida A, et al. Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia. Sci Rep  2017; 7(1): 4826.
[http://dx.doi.org/10.1038/s41598-017-05278-0] [PMID: 28684736] 
[166] 
Abe K, Uwagawa T, Haruki K, et al. Effects of ω-3 fatty acid supplementation in patients with bile duct or pancreatic cancer undergoing chemotherapy. Anticancer Res  2018; 38(4): 2369-75.
[PMID: 29599363] 
[167] 
Hanigan MH, Devarajan P. Cisplatin nephrotoxicity: molecular mechanisms. Cancer Ther  2003; 1: 47-61.
[PMID: 18185852] 
[168] 
Shi HH, Wang CC, Guo Y, Xue CH, Zhang TT, Wang YM. DHA-PC protects kidneys against cisplatin-induced toxicity and its underlying mechanisms in mice. Food Funct  2019; 10(3): 1571-81.
[http://dx.doi.org/10.1039/C8FO02386G] [PMID: 30806384] 
[169] 
Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol  2014; 740: 364-78.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905] 
[170] 
Naqshbandi A, Farooqui Z, Khan MW, et al. Fish oil supplementation ameliorates long term cisplatin treatment induced toxicity and oxidative damage in rat kidney. J Nephrol Ren Dis 1  2017; 2: 2.
[171] 
Li J, Hao Q, Cao W, Vadgama JV, Wu Y. Celecoxib in breast cancer prevention and therapy. Cancer Manag Res  2018; 10: 4653-67.
[http://dx.doi.org/10.2147/CMAR.S178567] [PMID: 30464589] 
[172] 
Blanke CD. Celecoxib with chemotherapy in colorectal cancer. Oncology (Williston Park)  2002; 16(4)(Suppl. 3): 17-21.
[PMID: 12014863] 
[173] 
Zhang W, Yi L, Shen J, Zhang H, Luo P, Zhang J. Comparison of the benefits of celecoxib combined with anticancer therapy in advanced non-small cell lung cancer: A meta-analysis. J Cancer  2020; 11(7): 1816-27.
[http://dx.doi.org/10.7150/jca.35003] [PMID: 32194793] 
[174] 
Negi AK, Renuka , Bhatnagar A, Agnihotri N. Celecoxib and fish oil: a combination strategy for decreased inflammatory mediators in early stages of experimental mammary cancer. Inflammopharmacology  2016; 24(1): 11-22.
[http://dx.doi.org/10.1007/s10787-015-0259-7] [PMID: 26749133] 
[175] 
Rani I, Vaiphei K, Agnihotri N. Supplementation of fish oil augments efficacy and attenuates toxicity of 5-fluorouracil in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium-induced colon carcinogenesis. Cancer Chemother Pharmacol  2014; 74(2): 309-22.
[http://dx.doi.org/10.1007/s00280-014-2497-6] [PMID: 24916547] 
[176] 
Hardman WE, Moyer MP, Cameron IL. Consumption of an omega-3 fatty acids product, INCELL AAFA, reduced side-effects of CPT-11 (irinotecan) in mice. Br J Cancer  2002; 86(6): 983-8.
[http://dx.doi.org/10.1038/sj.bjc.6600175] [PMID: 11953833] 
[177] 
Shen S, Unger JM, Crew KD, et al. Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927). Breast Cancer Res Treat  2018; 172(3): 603-10.
[http://dx.doi.org/10.1007/s10549-018-4946-0] [PMID: 30159789] 
[178] 
Crew KD, Greenlee H, Capodice J, et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol  2007; 25(25): 3877-83.
[http://dx.doi.org/10.1200/JCO.2007.10.7573] [PMID: 17761973] 
[179] 
Hershman DL, Unger JM, Crew KD, et al. Randomized multicenter placebo-controlled trial of omega-3 fatty acids for the control of aromatase inhibitor-induced musculoskeletal pain: SWOG S0927. J Clin Oncol  2015; 33(17): 1910-7.
[http://dx.doi.org/10.1200/JCO.2014.59.5595] [PMID: 25940724] 
[180] 
Hutchins-Wiese HL, Picho K, Watkins BA, et al. High-dose eicosapentaenoic acid and docosahexaenoic acid supplementation reduces bone resorption in postmenopausal breast cancer survivors on aromatase inhibitors: a pilot study. Nutr Cancer  2014; 66(1): 68-76.
[http://dx.doi.org/10.1080/01635581.2014.847964] [PMID: 24274259] 
[181] 
Bonatto SJ, Oliveira HH, Nunes EA, et al. Fish oil supplementation improves neutrophil function during cancer chemotherapy. Lipids  2012; 47(4): 383-9.
[http://dx.doi.org/10.1007/s11745-011-3643-0] [PMID: 22160495] 
[182] 
Ghoreishi Z, Esfahani A, Djazayeri A, et al. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial. BMC Cancer  2012; 12: 355.
[http://dx.doi.org/10.1186/1471-2407-12-355] [PMID: 22894640] 
[183] 
Werner K, Küllenberg de Gaudry D, Taylor LA, et al. Dietary supplementation with n-3-fatty acids in patients with pancreatic cancer and cachexia: marine phospholipids versus fish oil - a randomized controlled double-blind trial. Lipids Health Dis  2017; 16(1): 104-4.
[http://dx.doi.org/10.1186/s12944-017-0495-5] [PMID: 28578704] 
[184] 
Sorensen LS, Rasmussen HH, Aardestrup IV, et al. Rapid incorporation of ω-3 fatty acids into colonic tissue after oral supplementation in patients with colorectal cancer: a randomized, placebo-controlled intervention trial. JPEN J Parenter Enteral Nutr  2014; 38(5): 617-24.
[http://dx.doi.org/10.1177/0148607113491782] [PMID: 23788002] 
[185] 
Sorensen LS, Thorlacius-Ussing O, Rasmussen HH, et al. Effects of perioperative supplementation with omega-3 fatty acids on leukotriene B4 and leukotriene B5 production by stimulated neutrophils in patients with colorectal cancer: a randomized, placebo-controlled intervention trial. Nutrients  2014; 6(10): 4043-57.
[http://dx.doi.org/10.3390/nu6104043] [PMID: 25268838] 
[186] 
Zhang B, Wei G, Li R, et al. n-3 fatty acid-based parenteral nutrition improves postoperative recovery for cirrhotic patients with liver cancer: A randomized controlled clinical trial. Clin Nutr  2017; 36(5): 1239-44.
[http://dx.doi.org/10.1016/j.clnu.2016.08.002] [PMID: 27614675] 
[187] 
Bai H, Li Z, Meng Y, et al. Effects of parenteral ω-3 fatty acid supplementation in postoperative gastrointestinal cancer on immune function and length of hospital stay: a systematic review and meta-analysis. Asia Pac J Clin Nutr  2018; 27(1): 121-8.
[PMID: 29222889] 
[188] 
Angsutararux P, Luanpitpong S, Issaragrisil S. Chemotherapy-induced cardiotoxicity: Overview of the roles of oxidative stress. Oxid Med Cell Longev  2015; 2015: 795602.
[http://dx.doi.org/10.1155/2015/795602] [PMID: 26491536] 
[189] 
Cappetta D, De Angelis A, Sapio L, et al. Oxidative stress and cellular response to doxorubicin: A common factor in the complex milieu of anthracycline cardiotoxicity. Oxid Med Cell Longev  2017; 2017: 1521020.
[http://dx.doi.org/10.1155/2017/1521020] [PMID: 29181122] 
[190] 
Soni H, Kaminski D, Gangaraju R, Adebiyi A. Cisplatin-induced oxidative stress stimulates renal Fas ligand shedding. Ren Fail  2018; 40(1): 314-22.
[http://dx.doi.org/10.1080/0886022X.2018.1456938] [PMID: 29619879] 
[191] 
Pusztai L, Mendoza TR, Reuben JM, et al. Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine  2004; 25(3): 94-102.
[http://dx.doi.org/10.1016/j.cyto.2003.10.004] [PMID: 14698135] 
[192] 
Sakai C, Ishida M, Ohba H, et al. Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells. PLoS One  2017; 12(11): e0187934.
[http://dx.doi.org/10.1371/journal.pone.0187934] [PMID: 29121093] 
[193] 
Xu J, Feng ZP, Peng HY, Fu P. Omega-3 polyunsaturated fatty acids alleviate adenine-induced chronic renal failure via regulating ROS production and TGF-β/SMAD pathway. Eur Rev Med Pharmacol Sci  2018; 22(15): 5024-32.
[PMID: 30070341] 
[194] 
Clementi ME, Lazzarino G, Sampaolese B, Brancato A, Tringali G. DHA protects PC12 cells against oxidative stress and apoptotic signals through the activation of the NFE2L2/HO-1 axis. Int J Mol Med  2019; 43(6): 2523-31.
[http://dx.doi.org/10.3892/ijmm.2019.4170] [PMID: 31017264] 
[195] 
Li Q, Yu Q, Na R, Liu B. Omega-3 polyunsaturated fatty acids prevent murine dilated cardiomyopathy by reducing oxidative stress and cardiomyocyte apoptosis. Exp Ther Med  2017; 14(6): 6152-8.
[http://dx.doi.org/10.3892/etm.2017.5338] [PMID: 29285172] 
[196] 
Tulubas F, Gurel A, Oran M, Topcu B, Caglar V, Uygur E. The protective effects of ω-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats. Toxicol Ind Health  2015; 31(7): 638-44.
[http://dx.doi.org/10.1177/0748233713483203] [PMID: 23512535] 
[197] 
Uygur R, Aktas C, Tulubas F, Alpsoy S, Topcu B, Ozen OA. Cardioprotective effects of fish omega-3 fatty acids on doxorubicin-induced cardiotoxicity in rats. Hum Exp Toxicol  2014; 33(4): 435-45.
[http://dx.doi.org/10.1177/0960327113493304] [PMID: 24064909] 
[198] 
Uygur R, Aktas C, Tulubas F, et al. Protective effects of fish omega-3 fatty acids on doxorubicin-induced testicular apoptosis and oxidative damage in rats. Andrologia  2014; 46(8): 917-26.
[http://dx.doi.org/10.1111/and.12173] [PMID: 24117968] 
[199] 
Naqshbandi A, Khan MW, Rizwan S, Rehman SU, Khan F. Studies on the protective effect of dietary fish oil on cisplatin induced nephrotoxicity in rats. Food Chem Toxicol  2012; 50(2): 265-73.
[http://dx.doi.org/10.1016/j.fct.2011.10.039] [PMID: 22019697] 
[200] 
Hassan HA, Edrees GM, El-Gamel EM, El-Sayed EA. Amelioration of cisplatin-induced nephrotoxicity by grape seed extract and fish oil is mediated by lowering oxidative stress and DNA damage. Cytotechnology  2014; 66(3): 419-29.
[http://dx.doi.org/10.1007/s10616-013-9589-8] [PMID: 23761012] 
[201] 
Saleh D, Abdelbaset M, Hassan A, Sharaf O, Mahmoud S, Hegazy R. Omega-3 fatty acids ameliorate doxorubicin-induced cardiorenal toxicity: In-vivo regulation of oxidative stress, apoptosis and renal Nox4, and in-vitro preservation of the cytotoxic efficacy. PLoS One  2020; 15(11): e0242175.
[http://dx.doi.org/10.1371/journal.pone.0242175] [PMID: 33180794] 
[202] 
Zhelev Z, Ivanova D, Lazarova D, Aoki I, Bakalova R, Saga T. Docosahexaenoic acid sensitizes leukemia lymphocytes to barasertib and everolimus by ROS-dependent mechanism without affecting the level of ROS and viability of normal lymphocytes. Anticancer Res  2016; 36(4): 1673-82.
[PMID: 27069145] 
[203] 
Fukui M, Kang KS, Okada K, Zhu BT. EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. J Cell Biochem  2013; 114(1): 192-203.
[http://dx.doi.org/10.1002/jcb.24354] [PMID: 22903547] 
[204] 
Shin S, Jing K, Jeong S, et al. The omega-3 polyunsaturated fatty acid DHA induces simultaneous apoptosis and autophagy via mitochondrial ROS-mediated Akt-mTOR signaling in prostate cancer cells expressing mutant p53. BioMed Res Int  2013; 2013: 568671.
[http://dx.doi.org/10.1155/2013/568671] [PMID: 23841076] 
[205] 
Song EA, Kim H. Docosahexaenoic acid induces oxidative dna damage and apoptosis, and enhances the chemosensitivity of cancer cells. Int J Mol Sci  2016; 17(8): 1257.
[http://dx.doi.org/10.3390/ijms17081257] [PMID: 27527148] 
[206] 
Xue H, Ren W, Denkinger M, Schlotzer E, Wischmeyer PE. Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω-3 Polyunsaturated Fatty Acids. JPEN J Parenter Enteral Nutr  2016; 40(1): 52-66.
[http://dx.doi.org/10.1177/0148607115581838] [PMID: 25888676] 
[207] 
Dijk FJ, van Dijk M, Dorresteijn B, van Norren K. DPA shows comparable chemotherapy sensitizing effects as EPA upon cellular incorporation in tumor cells. Oncotarget  2019; 10(57): 5983-92.
[http://dx.doi.org/10.18632/oncotarget.27236] [PMID: 31666929] 
[208] 
Chen J, Garssen J, Redegeld F. The efficacy of bortezomib in human multiple myeloma cells is enhanced by combination with omega-3 fatty acids DHA and EPA: Timing is essential. Clin Nutr  2021; 40(4): 1942-53.
[PMID: 32977994] 
[209] 
Guffy MM, North JA, Burns CP. Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells. Cancer Res  1984; 44(5): 1863-6.
[PMID: 6231987] 
[210] 
Mansour M, van Ginkel S, Dennis JC, et al. The combination of omega-3 stearidonic acid and docetaxel enhances cell death over docetaxel alone in human prostate cancer cells. J Cancer  2018; 9(23): 4536-46.
[http://dx.doi.org/10.7150/jca.26681] [PMID: 30519360] 
[211] 
Sheng H, Chen X, Liu B, Li P, Cao W. Omega-3 polyunsaturated fatty acids enhance cisplatin efficacy in gastric cancer cells by inducing apoptosis via ADORA1. Anticancer Agents Med Chem  2016; 16(9): 1085-92.
[http://dx.doi.org/10.2174/1871520616666160330104413] [PMID: 27025656] 
[212] 
Manda K, Kriesen S, Hildebrandt G, Fietkau R, Klautke G. Omega-3 fatty acid supplementation in cancer therapy : does eicosapentanoic acid influence the radiosensitivity of tumor cells? Strahlenther Onkol  2011; 187(2): 127-34.
[http://dx.doi.org/10.1007/s00066-010-2166-6] [PMID: 21267532] 
[213] 
Wang F, Bhat K, Doucette M, et al. Docosahexaenoic acid (DHA) sensitizes brain tumor cells to etoposide-induced apoptosis. Curr Mol Med  2011; 11(6): 503-11.
[http://dx.doi.org/10.2174/156652411796268740] [PMID: 21663587] 
[214] 
Chauvin L, Goupille C, Blanc C, et al. Long chain n-3 polyunsaturated fatty acids increase the efficacy of docetaxel in mammary cancer cells by downregulating Akt and PKCε/δ-induced ERK pathways. Biochim Biophys Acta  2016; 1861(4): 380-90.
[http://dx.doi.org/10.1016/j.bbalip.2016.01.012] [PMID: 26821209] 
[215] 
Guo CH, Hsia S, Chung CH, et al. Combination of fish oil and selenium enhances anticancer efficacy and targets multiple signaling pathways in Anti-VEGF agent treated-TNBC tumor-bearing mice. Mar Drugs  2021; 19(4): 193.
[http://dx.doi.org/10.3390/md19040193] [PMID: 33805447] 
[216] 
de la Rosa Oliva F, Meneses García A, Ruiz Calzada H, et al. Effects of omega-3 fatty acids supplementation on neoadjuvant chemotherapy-induced toxicity in patients with locally advanced breast cancer: a randomized, controlled, double-blinded clinical trial. Nutr Hosp  2019; 36(4): 769-76.
[http://dx.doi.org/10.20960/nh.2338] [PMID: 31192682] 
[217] 
Song M, Ou FS, Zemla TJ, et al. Marine omega-3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance). Int J Cancer  2019; 145(2): 380-9.
[http://dx.doi.org/10.1002/ijc.32113] [PMID: 30623420] 
[218] 
Miyata H, Yano M, Yasuda T, et al. Randomized study of the clinical effects of ω-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer. Nutrition  2017; 33: 204-10.
[http://dx.doi.org/10.1016/j.nut.2016.07.004] [PMID: 27644137] 
[219] 
Golkhalkhali B, Rajandram R, Paliany AS, et al. Strain-specific probiotic (microbial cell preparation) and omega-3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial. Asia Pac J Clin Oncol  2018; 14(3): 179-91.
[http://dx.doi.org/10.1111/ajco.12758] [PMID: 28857425] 
[220] 
Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Randomized study of the effect of vitamin D and omega-3 fatty acids cosupplementation as adjuvant chemotherapy on inflammation and nutritional status in colorectal cancer patients. J Diet Suppl  2020; 17(4): 384-400.
[http://dx.doi.org/10.1080/19390211.2019.1600096] [PMID: 31106659] 
[221] 
Hashemipour MA, Barzegari S, Kakoie S, Aghahi RH. Effects of omega-3 fatty acids against chemotherapy-induced mucositis: A double-blind randomized clinical trial. Wounds  2017; 29(12): 360-6.
[PMID: 29324423] 
[222] 
Aredes MA, da Camara AO, de Paula NS, Fraga KYD, do Carmo MDGT, Chaves GV. Efficacy of ω-3 supplementation on nutritional status, skeletal muscle, and chemoradiotherapy toxicity in cervical cancer patients: A randomized, triple-blind, clinical trial conducted in a middle-income country. Nutrition  2019; 67-68: 110528.
[http://dx.doi.org/10.1016/j.nut.2019.06.009] [PMID: 31445316] 
[223] 
Eltweri AM, Thomas AL, Chung WY, et al. The effect of supplementary omegaven® on the clinical outcome of patients with advanced esophagogastric adenocarcinoma receiving palliative epirubicin, oxaliplatin, and capecitabine chemotherapy: A phase II clinical trial. Anticancer Res  2019; 39(2): 853-61.
[http://dx.doi.org/10.21873/anticanres.13185] [PMID: 30711967] 
[224] 
van der Meij BS, Langius JA, Smit EF, et al. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J Nutr  2010; 140(10): 1774-80.
[http://dx.doi.org/10.3945/jn.110.121202] [PMID: 20739445] 
[225] 
van der Meij BS, Langius JA, Spreeuwenberg MD, et al. Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: an RCT. Eur J Clin Nutr  2012; 66(3): 399-404.
[http://dx.doi.org/10.1038/ejcn.2011.214] [PMID: 22234041] 
[226] 
Finocchiaro C, Segre O, Fadda M, et al. Effect of n-3 fatty acids on patients with advanced lung cancer: a double-blind, placebo-controlled study. Br J Nutr  2012; 108(2): 327-33.
[http://dx.doi.org/10.1017/S0007114511005551] [PMID: 22114792] 
[227] 
Fietkau R, Lewitzki V, Kuhnt T, et al. A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial. Cancer  2013; 119(18): 3343-53.
[http://dx.doi.org/10.1002/cncr.28197] [PMID: 23765693] 
[228] 
Camargo CQ, Mocellin MC, Brunetta HS, et al. Fish oil decreases the severity of treatment-related adverse events in gastrointestinal cancer patients undergoing chemotherapy: A randomized, placebo-controlled, triple-blind clinical trial. Clin Nutr ESPEN  2019; 31: 61-70.
[http://dx.doi.org/10.1016/j.clnesp.2019.02.015] [PMID: 31060836] 
[229] 
Miyata H, Yano M, Yasuda T, et al. Randomized study of clinical effect of enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer. Clin Nutr  2012; 31(3): 330-6.
[http://dx.doi.org/10.1016/j.clnu.2011.11.002] [PMID: 22169459] 
[230] 
Silva JdeA, Trindade EB, Fabre ME, et al. Fish oil supplement alters markers of inflammatory and nutritional status in colorectal cancer patients. Nutr Cancer  2012; 64(2): 267-73.
[http://dx.doi.org/10.1080/01635581.2012.643133] [PMID: 22295891] 
[231] 
Martínez N, Herrera M, Frías L, et al. A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study. Clin Transl Oncol  2019; 21(4): 489-98.
[http://dx.doi.org/10.1007/s12094-018-1950-0] [PMID: 30293230] 
Cite As
Current Drug Targets

Omega-3 Fatty Acid Treatment Combined with Chemotherapy to Prevent Toxicity, Drug Resistance, and Metastasis in Cancer

Abstract

Graphical Abstract
