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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Tasnim Zahan, Plabon K. Das, Syeda F. Akter, Rowshanul Habib, Md. Habibur Rahman, Md. Rezaul Karim* and Farhadul Islam*

DOI: 10.2174/1871520620999200730161829

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Therapy Resistance in Cancers: Phenotypic, Metabolic, Epigenetic and Tumour Microenvironmental Perspectives

Page: [2190 - 2206] Pages: 17

  • * (Excluding Mailing and Handling)

Abstract

Background: Chemoresistance is a vital problem in cancer therapy where cancer cells develop mechanisms to encounter the effect of chemotherapeutics, resulting in cancer recurrence. In addition, chemotherapy- resistant leads to the formation of a more aggressive form of cancer cells, which, in turn, contributes to the poor survival of patients with cancer.

Objective: In this review, we aimed to provide an overview of how the therapy resistance property evolves in cancer cells, contributing factors and their role in cancer chemoresistance, and exemplified the problems of some available therapies.

Methods: The published literature on various electronic databases including, Pubmed, Scopus, Google scholar containing keywords cancer therapy resistance, phenotypic, metabolic and epigenetic factors, were vigorously searched, retrieved and analyzed.

Results: Cancer cells have developed a range of cellular processes, including uncontrolled activation of Epithelial- Mesenchymal Transition (EMT), metabolic reprogramming and epigenetic alterations. These cellular processes play significant roles in the generation of therapy resistance. Furthermore, the microenvironment where cancer cells evolve effectively contributes to the process of chemoresistance. In tumour microenvironment immune cells, Mesenchymal Stem Cells (MSCs), endothelial cells and cancer-associated fibroblasts (CAFs) contribute to the maintenance of therapy-resistant phenotype via the secretion of factors that promote resistance to chemotherapy.

Conclusion: To conclude, as these factors hinder successful cancer therapies, therapeutic resistance property of cancer cells is a subject of intense research, which in turn could open a new horizon to aim for developing efficient therapies.

Keywords: Therapy resistance, EMT, metabolic reprogramming, cancer heterogeneity, tumour microenvironment, therapeutic options.

Graphical Abstract

[1]
Gatenby, R.; Brown, J. The evolution and ecology of resistance in cancer therapy. Cold Spring Harb. Perspect. Med., 2018, 8(3)a033415
[http://dx.doi.org/10.1101/cshperspect.a033415] [PMID: 28710258]
[2]
Galletti, G.; Leach, B.I.; Lam, L.; Tagawa, S.T. Mechanisms of resistance to systemic therapy in metastatic castration-resistant prostate cancer. Cancer Treat. Rev., 2017, 57, 16-27.
[http://dx.doi.org/10.1016/j.ctrv.2017.04.008] [PMID: 28527407]
[3]
Das, P.K.; Zahan, T.; Abdur Rakib, M.; Khanam, J.A.; Pillai, S.; Islam, F. Natural compounds targeting cancer stem cells: A promising resource for chemotherapy. Anticancer. Agents Med. Chem., 2019, 19(15), 1796-1808.
[http://dx.doi.org/10.2174/1871520619666190704111714] [PMID: 31272363]
[4]
Chang, A. Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer, 2011, 71(1), 3-10.
[http://dx.doi.org/10.1016/j.lungcan.2010.08.022] [PMID: 20951465]
[5]
Haslehurst, A.M.; Koti, M.; Dharsee, M.; Nuin, P.; Evans, K.; Geraci, J.; Childs, T.; Chen, J.; Li, J.; Weberpals, J.; Davey, S.; Squire, J.; Park, P.C.; Feilotter, H. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer, 2012, 12(1), 91.
[http://dx.doi.org/10.1186/1471-2407-12-91] [PMID: 22429801]
[6]
Indran, I.R.; Tufo, G.; Pervaiz, S.; Brenner, C. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim. Biophys. Acta, 2011, 1807(6), 735-745.
[http://dx.doi.org/10.1016/j.bbabio.2011.03.010] [PMID: 21453675]
[7]
Sava, G.P.; Fan, H.; Fisher, R.A.; Lusvarghi, S.; Pancholi, S.; Ambudkar, S.V.; Martin, L.A.; Charles Coombes, R.; Buluwela, L.; Ali, S. ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942. Oncogene, 2020, 39(3), 651-663.
[http://dx.doi.org/10.1038/s41388-019-1008-y] [PMID: 31530935]
[8]
Zhang, P.; Wei, Y.; Wang, L.; Debeb, B.G.; Yuan, Y.; Zhang, J.; Yuan, J.; Wang, M.; Chen, D.; Sun, Y.; Woodward, W.A.; Liu, Y.; Dean, D.C.; Liang, H.; Hu, Y.; Ang, K.K.; Hung, M.C.; Chen, J.; Ma, L. ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1. Nat. Cell Biol., 2014, 16(9), 864-875.
[http://dx.doi.org/10.1038/ncb3013] [PMID: 25086746]
[9]
Das, P.K.; Pillai, S.; Rakib, M.A.; Khanam, J.A.; Gopalan, V.; Lam, A.K.Y.; Islam, F. Plasticity of cancer stem cell: Origin and role in disease progression and therapy resistance. Stem Cell Rev. Rep., 2020, 16(2), 397-412.
[http://dx.doi.org/10.1007/s12015-019-09942-y] [PMID: 31965409]
[10]
Creighton, C.J.; Li, X.; Landis, M.; Dixon, J.M.; Neumeister, V.M.; Sjolund, A.; Rimm, D.L.; Wong, H.; Rodriguez, A.; Herschkowitz, J.I.; Fan, C.; Zhang, X.; He, X.; Pavlick, A.; Gutierrez, M.C.; Renshaw, L.; Larionov, A.A.; Faratian, D.; Hilsenbeck, S.G.; Perou, C.M.; Lewis, M.T.; Rosen, J.M.; Chang, J.C. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc. Natl. Acad. Sci. USA, 2009, 106(33), 13820-13825.
[http://dx.doi.org/10.1073/pnas.0905718106] [PMID: 19666588]
[11]
Ahmed, F.; Haass, N.K. Microenvironment-driven dynamic heterogeneity and phenotypic plasticity as a mechanism of melanoma therapy resistance. Front. Oncol., 2018, 8, 173.
[http://dx.doi.org/10.3389/fonc.2018.00173] [PMID: 29881716]
[12]
Ruocco, M.R.; Avagliano, A.; Granato, G.; Vigliar, E.; Masone, S.; Montagnani, S.; Arcucci, A. Metabolic flexibility in melanoma: A potential therapeutic target. Semin. Cancer Biol., 2019, 59, 187-207.
[http://dx.doi.org/10.1016/j.semcancer.2019.07.016]
[13]
Wainwright, E.N.; Scaffidi, P. Epigenetics and cancer stem cells: Unleashing, hijacking, and restricting cellular plasticity. Trends Cancer, 2017, 3(5), 372-386.
[http://dx.doi.org/10.1016/j.trecan.2017.04.004] [PMID: 28718414]
[14]
Yamada, D.; Kobayashi, S.; Wada, H.; Kawamoto, K.; Marubashi, S.; Eguchi, H.; Ishii, H.; Nagano, H.; Doki, Y.; Mori, M. Role of crosstalk between interleukin-6 and transforming growth factor-beta 1 in epithelial-mesenchymal transition and chemoresistance in biliary tract cancer. Eur. J. Cancer, 2013, 49(7), 1725-1740.
[http://dx.doi.org/10.1016/j.ejca.2012.12.002] [PMID: 23298711]
[15]
Boelens, M.C.; Wu, T.J.; Nabet, B.Y.; Xu, B.; Qiu, Y.; Yoon, T.; Azzam, D.J.; Twyman-Saint Victor, C.; Wiemann, B.Z.; Ishwaran, H.; Ter Brugge, P.J.; Jonkers, J.; Slingerland, J.; Minn, A.J. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell, 2014, 159(3), 499-513.
[http://dx.doi.org/10.1016/j.cell.2014.09.051] [PMID: 25417103]
[16]
Yu, Y.; Xiao, C.H.; Tan, L.D.; Wang, Q.S.; Li, X.Q.; Feng, Y.M. Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-β signalling. Br. J. Cancer, 2014, 110(3), 724-732.
[http://dx.doi.org/10.1038/bjc.2013.768] [PMID: 24335925]
[17]
Joseph, J.P.; Harishankar, M.K.; Pillai, A.A.; Devi, A. Hypoxia induced EMT: A review on the mechanism of tumor progression and metastasis in OSCC. Oral Oncol., 2018, 80, 23-32.
[http://dx.doi.org/10.1016/j.oraloncology.2018.03.004] [PMID: 29706185]
[18]
Aleksakhina, S.N.; Kashyap, A.; Imyanitov, E.N. Mechanisms of acquired tumor drug resistance. Biochim. Biophys. Acta Rev. Cancer, 2019, 1872(2)188310
[http://dx.doi.org/10.1016/j.bbcan.2019.188310] [PMID: 31442474]
[19]
Gerdes, M.J.; Sood, A.; Sevinsky, C.; Pris, A.D.; Zavodszky, M.I.; Ginty, F. Emerging understanding of multiscale tumor heterogeneity. Front. Oncol., 2014, 4, 366.
[http://dx.doi.org/10.3389/fonc.2014.00366] [PMID: 25566504]
[20]
Gerlinger, M.; Rowan, A.J.; Horswell, S.; Math, M.; Larkin, J.; Endesfelder, D.; Gronroos, E.; Martinez, P.; Matthews, N.; Stewart, A.; Tarpey, P.; Varela, I.; Phillimore, B.; Begum, S.; McDonald, N.Q.; Butler, A.; Jones, D.; Raine, K.; Latimer, C.; Santos, C.R.; Nohadani, M.; Eklund, A.C.; Spencer-Dene, B.; Clark, G.; Pickering, L.; Stamp, G.; Gore, M.; Szallasi, Z.; Downward, J.; Futreal, P.A.; Swanton, C. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med., 2012, 366(10), 883-892.
[http://dx.doi.org/10.1056/NEJMoa1113205] [PMID: 22397650]
[21]
Burrell, R.A.; McGranahan, N.; Bartek, J.; Swanton, C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature, 2013, 501(7467), 338-345.
[http://dx.doi.org/10.1038/nature12625] [PMID: 24048066]
[22]
Dick, J.E. Stem cell concepts renew cancer research. Blood, 2008, 112(13), 4793-4807.
[http://dx.doi.org/10.1182/blood-2008-08-077941] [PMID: 19064739]
[23]
Nowell, P.C. The clonal evolution of tumor cell populations. Science, 1976, 194(4260), 23-28.
[http://dx.doi.org/10.1126/science.959840] [PMID: 959840]
[24]
Pietras, A. Cancer stem cells in tumor heterogeneity. Adv. Cancer Res., 2011, 112, 255-281.
[http://dx.doi.org/10.1016/B978-0-12-387688-1.00009-0] [PMID: 21925307]
[25]
Reya, T.; Morrison, S.J.; Clarke, M.F.; Weissman, I.L. Stem cells, cancer, and cancer stem cells. Nature, 2001, 414(6859), 105-111.
[http://dx.doi.org/10.1038/35102167] [PMID: 11689955]
[26]
Marusyk, A.; Polyak, K. Tumor heterogeneity: Causes and consequences. Biochim. Biophys. Acta, 2010, 1805(1), 105-117.
[PMID: 19931353]
[27]
Wang, Z.; Liu, Z.; Wu, X.; Chu, S.; Wang, J.; Yuan, H.; Roth, M.; Yuan, Y.C.; Bhatia, R.; Chen, W. ATRA-induced cellular differentiation and CD38 expression inhibits acquisition of BCR-ABL mutations for CML acquired resistance. PLoS Genet., 2014, 10(6)e1004414
[http://dx.doi.org/10.1371/journal.pgen.1004414] [PMID: 24967705]
[28]
Shah, N.P.; Skaggs, B.J.; Branford, S.; Hughes, T.P.; Nicoll, J.M.; Paquette, R.L.; Sawyers, C.L. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J. Clin. Invest., 2007, 117(9), 2562-2569.
[http://dx.doi.org/10.1172/JCI30890] [PMID: 17710227]
[29]
Calabretta, B.; Perrotti, D. The biology of CML blast crisis. Blood, 2004, 103(11), 4010-4022.
[http://dx.doi.org/10.1182/blood-2003-12-4111] [PMID: 14982876]
[30]
Cabrera, M.C.; Hollingsworth, R.E.; Hurt, E.M. Cancer stem cell plasticity and tumor hierarchy. World J. Stem Cells, 2015, 7(1), 27-36.
[http://dx.doi.org/10.4252/wjsc.v7.i1.27] [PMID: 25621103]
[31]
O’Connell, M.P.; Marchbank, K.; Webster, M.R.; Valiga, A.A.; Kaur, A.; Vultur, A.; Li, L.; Herlyn, M.; Villanueva, J.; Liu, Q.; Yin, X.; Widura, S.; Nelson, J.; Ruiz, N.; Camilli, T.C.; Indig, F.E.; Flaherty, K.T.; Wargo, J.A.; Frederick, D.T.; Cooper, Z.A.; Nair, S.; Amaravadi, R.K.; Schuchter, L.M.; Karakousis, G.C.; Xu, W.; Xu, X.; Weeraratna, A.T. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Discov., 2013, 3(12), 1378-1393.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0005] [PMID: 24104062]
[32]
Garg, M. Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance. World J. Stem Cells, 2017, 9(8), 118-126.
[http://dx.doi.org/10.4252/wjsc.v9.i8.118] [PMID: 28928908]
[33]
Thiery, J.P. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer, 2002, 2(6), 442-454.
[http://dx.doi.org/10.1038/nrc822] [PMID: 12189386]
[34]
Kim, W.Y.; Perera, S.; Zhou, B.; Carretero, J.; Yeh, J.J.; Heathcote, S.A.; Jackson, A.L.; Nikolinakos, P.; Ospina, B.; Naumov, G.; Brandstetter, K.A.; Weigman, V.J.; Zaghlul, S.; Hayes, D.N.; Padera, R.F.; Heymach, J.V.; Kung, A.L.; Sharpless, N.E.; Kaelin, W.G., Jr; Wong, K.K. HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J. Clin. Invest., 2009, 119(8), 2160-2170.
[http://dx.doi.org/10.1172/JCI38443] [PMID: 19662677]
[35]
Kawai, T.; Yasuchika, K.; Ishii, T.; Katayama, H.; Yoshitoshi, E.Y.; Ogiso, S.; Kita, S.; Yasuda, K.; Fukumitsu, K.; Mizumoto, M.; Hatano, E.; Uemoto, S. Keratin 19, a cancer stem cell marker in human hepatocellular carcinoma. Clin. Cancer Res., 2015, 21(13), 3081-3091.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1936] [PMID: 25820415]
[36]
Liu, L.; Dai, Y.; Chen, J.; Zeng, T.; Li, Y.; Chen, L.; Zhu, Y.H.; Li, J.; Li, Y.; Ma, S.; Xie, D.; Yuan, Y.F.; Guan, X.Y. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3β/Snail signaling. Hepatology, 2014, 59(2), 531-543.
[http://dx.doi.org/10.1002/hep.26677] [PMID: 23929794]
[37]
Richard, G.; Dalle, S.; Monet, M.A.; Ligier, M.; Boespflug, A.; Pommier, R.M.; de la Fouchardière, A.; Perier-Muzet, M.; Depaepe, L.; Barnault, R.; Tondeur, G.; Ansieau, S.; Thomas, E.; Bertolotto, C.; Ballotti, R.; Mourah, S.; Battistella, M.; Lebbé, C.; Thomas, L.; Puisieux, A.; Caramel, J. ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors. EMBO Mol. Med., 2016, 8(10), 1143-1161.
[http://dx.doi.org/10.15252/emmm.201505971] [PMID: 27596438]
[38]
Sonveaux, P.; Végran, F.; Schroeder, T.; Wergin, M.C.; Verrax, J.; Rabbani, Z.N.; De Saedeleer, C.J.; Kennedy, K.M.; Diepart, C.; Jordan, B.F.; Kelley, M.J.; Gallez, B.; Wahl, M.L.; Feron, O.; Dewhirst, M.W. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Invest., 2008, 118(12), 3930-3942.
[http://dx.doi.org/10.1172/JCI36843] [PMID: 19033663]
[39]
Thomson, S.; Petti, F.; Sujka-Kwok, I.; Epstein, D.; Haley, J.D. Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy. Clin. Exp. Metastasis, 2008, 25(8), 843-854.
[http://dx.doi.org/10.1007/s10585-008-9200-4] [PMID: 18696232]
[40]
Oliveras-Ferraros, C.; Corominas-Faja, B.; Cufí, S.; Vazquez-Martin, A.; Martin-Castillo, B.; Iglesias, J.M.; López-Bonet, E.; Martin, Á.G.; Menendez, J.A. Epithelial-to-Mesenchymal Transition (EMT) confers primary resistance to trastuzumab (Herceptin). Cell Cycle, 2012, 11(21), 4020-4032.
[http://dx.doi.org/10.4161/cc.22225] [PMID: 22992620]
[41]
Parkin, B.; Ouillette, P.; Li, Y.; Keller, J.; Lam, C.; Roulston, D.; Li, C.; Shedden, K.; Malek, S.N. Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia. Blood, 2013, 121(2), 369-377.
[http://dx.doi.org/10.1182/blood-2012-04-427039] [PMID: 23175688]
[42]
Navin, N.; Krasnitz, A.; Rodgers, L.; Cook, K.; Meth, J.; Kendall, J.; Riggs, M.; Eberling, Y.; Troge, J.; Grubor, V.; Levy, D.; Lundin, P.; Månér, S.; Zetterberg, A.; Hicks, J.; Wigler, M. Inferring tumor progression from genomic heterogeneity. Genome Res., 2010, 20(1), 68-80.
[http://dx.doi.org/10.1101/gr.099622.109] [PMID: 19903760]
[43]
Coller, H.A. Is cancer a metabolic disease? Am. J. Pathol., 2014, 184(1), 4-17.
[http://dx.doi.org/10.1016/j.ajpath.2013.07.035] [PMID: 24139946]
[44]
Moreno-Sánchez, R.; Rodríguez-Enríquez, S.; Marín-Hernández, A.; Saavedra, E. Energy metabolism in tumor cells. FEBS J., 2007, 274(6), 1393-1418.
[http://dx.doi.org/10.1111/j.1742-4658.2007.05686.x] [PMID: 17302740]
[45]
Avagliano, A.; Ruocco, M.R.; Aliotta, F.; Belviso, I.; Accurso, A.; Masone, S.; Montagnani, S.; Arcucci, A. Mitochondrial flexibility of breast cancers: A growth advantage and a therapeutic opportunity. Cells, 2019, 8(5), 401.
[http://dx.doi.org/10.3390/cells8050401] [PMID: 31052256]
[46]
Whitaker-Menezes, D.; Martinez-Outschoorn, U.E.; Flomenberg, N.; Birbe, R.C.; Witkiewicz, A.K.; Howell, A.; Pavlides, S.; Tsirigos, A.; Ertel, A.; Pestell, R.G.; Broda, P.; Minetti, C.; Lisanti, M.P.; Sotgia, F. Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: Visualizing the therapeutic effects of metformin in tumor tissue. Cell Cycle, 2011, 10(23), 4047-4064.
[http://dx.doi.org/10.4161/cc.10.23.18151] [PMID: 22134189]
[47]
Martinez-Outschoorn, U.E.; Peiris-Pagés, M.; Pestell, R.G.; Sotgia, F.; Lisanti, M.P. Cancer metabolism: A therapeutic perspective. Nat. Rev. Clin. Oncol., 2017, 14(1), 11-31.
[http://dx.doi.org/10.1038/nrclinonc.2016.60] [PMID: 27141887]
[48]
Eales, K.L.; Hollinshead, K.E.; Tennant, D.A. Hypoxia and metabolic adaptation of cancer cells. Oncogenesis, 2016, 5e190
[http://dx.doi.org/10.1038/oncsis.2015.50] [PMID: 26807645]
[49]
Pavlova, N.N.; Thompson, C.B. The emerging hallmarks of cancer metabolism. Cell Metab., 2016, 23(1), 27-47.
[http://dx.doi.org/10.1016/j.cmet.2015.12.006] [PMID: 26771115]
[50]
Cairns, R.A.; Harris, I.S.; Mak, T.W. Regulation of cancer cell metabolism. Nat. Rev. Cancer, 2011, 11(2), 85-95.
[http://dx.doi.org/10.1038/nrc2981] [PMID: 21258394]
[51]
Badri, H.; Leder, K. Optimal treatment and stochastic modeling of heterogeneous tumors. Biol. Direct, 2016, 11, 40.
[http://dx.doi.org/10.1186/s13062-016-0142-5] [PMID: 27549860]
[52]
Lee, S.Y.; Jeong, E.K.; Ju, M.K.; Jeon, H.M.; Kim, M.Y.; Kim, C.H.; Park, H.G.; Han, S.I.; Kang, H.S. Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol. Cancer, 2017, 16(1), 10.
[http://dx.doi.org/10.1186/s12943-016-0577-4] [PMID: 28137309]
[53]
Cuyàs, E.; Corominas-Faja, B.; Menendez, J.A. The nutritional phenome of EMT-induced cancer stem-like cells. Oncotarget, 2014, 5(12), 3970-3982.
[http://dx.doi.org/10.18632/oncotarget.2147] [PMID: 24994116]
[54]
Kim, I.S.; Heilmann, S.; Kansler, E.R.; Zhang, Y.; Zimmer, M.; Ratnakumar, K.; Bowman, R.L.; Simon-Vermot, T.; Fennell, M.; Garippa, R.; Lu, L.; Lee, W.; Hollmann, T.; Xavier, J.B.; White, R.M. Microenvironment-derived factors driving metastatic plasticity in melanoma. Nat. Commun., 2017, 8, 14343.
[http://dx.doi.org/10.1038/ncomms14343] [PMID: 28181494]
[55]
Pradelli, L.A.; Bénéteau, M.; Chauvin, C.; Jacquin, M.A.; Marchetti, S.; Muñoz-Pinedo, C.; Auberger, P.; Pende, M.; Ricci, J.E. Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation. Oncogene, 2010, 29(11), 1641-1652.
[http://dx.doi.org/10.1038/onc.2009.448] [PMID: 19966861]
[56]
Podar, K.; Gouill, S.L.; Zhang, J.; Opferman, J.T.; Zorn, E.; Tai, Y.T.; Hideshima, T.; Amiot, M.; Chauhan, D.; Harousseau, J.L.; Anderson, K.C. A pivotal role for Mcl-1 in Bortezomib-induced apoptosis. Oncogene, 2008, 27(6), 721-731.
[http://dx.doi.org/10.1038/sj.onc.1210679] [PMID: 17653083]
[57]
Liu, Z.; Xu, J.; He, J.; Zheng, Y.; Li, H.; Lu, Y.; Qian, J.; Lin, P.; Weber, D.M.; Yang, J.; Yi, Q. A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance. Blood, 2014, 124(13), 2061-2071.
[http://dx.doi.org/10.1182/blood-2014-03-557298] [PMID: 25049282]
[58]
Pepper, C.; Hoy, T.; Bentley, D.P. Bcl-2/Bax ratios in chronic lymphocytic leukaemia and their correlation with in vitro apoptosis and clinical resistance. Br. J. Cancer, 1997, 76(7), 935-938.
[http://dx.doi.org/10.1038/bjc.1997.487] [PMID: 9328155]
[59]
Zhao, Y.; Altman, B.J.; Coloff, J.L.; Herman, C.E.; Jacobs, S.R.; Wieman, H.L.; Wofford, J.A.; Dimascio, L.N.; Ilkayeva, O.; Kelekar, A.; Reya, T.; Rathmell, J.C. Glycogen synthase kinase 3α and 3β mediate a glucose-sensitive antiapoptotic signaling pathway to stabilize Mcl-1. Mol. Cell. Biol., 2007, 27(12), 4328-4339.
[http://dx.doi.org/10.1128/MCB.00153-07] [PMID: 17371841]
[60]
Woo, Y.M.; Shin, Y.; Lee, E.J.; Lee, S.; Jeong, S.H.; Kong, H.K.; Park, E.Y.; Kim, H.K.; Han, J.; Chang, M.; Park, J.H. Inhibition of aerobic glycolysis represses Akt/mTOR/HIF-1α axis and restores tamoxifen sensitivity in antiestrogen-resistant breast cancer cells. PLoS One, 2015, 10(7)e0132285
[http://dx.doi.org/10.1371/journal.pone.0132285] [PMID: 26158266]
[61]
Zhang, X.Y.; Zhang, M.; Cong, Q.; Zhang, M.X.; Zhang, M.Y.; Lu, Y.Y.; Xu, C.J. Hexokinase 2 confers resistance to cisplatin in ovarian cancer cells by enhancing cisplatin-induced autophagy. Int. J. Biochem. Cell Biol., 2018, 95, 9-16.
[http://dx.doi.org/10.1016/j.biocel.2017.12.010] [PMID: 29247711]
[62]
Grasso, C.; Jansen, G.; Giovannetti, E. Drug resistance in pancreatic cancer: Impact of altered energy metabolism. Crit. Rev. Oncol. Hematol., 2017, 114, 139-152.
[http://dx.doi.org/10.1016/j.critrevonc.2017.03.026] [PMID: 28477742]
[63]
Min, J.W.; Kim, K.I.; Kim, H.A.; Kim, E.K.; Noh, W.C.; Jeon, H.B.; Cho, D.H.; Oh, J.S.; Park, I.C.; Hwang, S.G.; Kim, J.S. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells. Biochem. Biophys. Res. Commun., 2013, 440(1), 137-142.
[http://dx.doi.org/10.1016/j.bbrc.2013.09.041] [PMID: 24051093]
[64]
Polimeni, M.; Voena, C.; Kopecka, J.; Riganti, C.; Pescarmona, G.; Bosia, A.; Ghigo, D. Modulation of doxorubicin resistance by the glucose-6-phosphate dehydrogenase activity. Biochem. J., 2011, 439(1), 141-149.
[http://dx.doi.org/10.1042/BJ20102016] [PMID: 21679161]
[65]
Catanzaro, D.; Gaude, E.; Orso, G.; Giordano, C.; Guzzo, G.; Rasola, A.; Ragazzi, E.; Caparrotta, L.; Frezza, C.; Montopoli, M. Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death. Oncotarget, 2015, 6(30), 30102-30114.
[http://dx.doi.org/10.18632/oncotarget.4945] [PMID: 26337086]
[66]
Bhanot, H.; Weisberg, E.L.; Reddy, M.M.; Nonami, A.; Neuberg, D.; Stone, R.M.; Podar, K.; Salgia, R.; Griffin, J.D.; Sattler, M. Acute myeloid leukemia cells require 6-phosphogluconate dehydrogenase for cell growth and NADPH-dependent metabolic reprogramming. Oncotarget, 2017, 8(40), 67639-67650.
[http://dx.doi.org/10.18632/oncotarget.18797] [PMID: 28978059]
[67]
Dong, C.; Yuan, T.; Wu, Y.; Wang, Y.; Fan, T.W.; Miriyala, S.; Lin, Y.; Yao, J.; Shi, J.; Kang, T.; Lorkiewicz, P.; St Clair, D.; Hung, M.C.; Evers, B.M.; Zhou, B.P. Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer Cell, 2013, 23(3), 316-331.
[http://dx.doi.org/10.1016/j.ccr.2013.01.022] [PMID: 23453623]
[68]
Shen, Y.A.; Wang, C.Y.; Hsieh, Y.T.; Chen, Y.J.; Wei, Y.H. Metabolic reprogramming orchestrates cancer stem cell properties in nasopharyngeal carcinoma. Cell Cycle, 2015, 14(1), 86-98.
[http://dx.doi.org/10.4161/15384101.2014.974419] [PMID: 25483072]
[69]
Sancho, P.; Barneda, D.; Heeschen, C. Hallmarks of cancer stem cell metabolism. Br. J. Cancer, 2016, 114(12), 1305-1312.
[http://dx.doi.org/10.1038/bjc.2016.152] [PMID: 27219018]
[70]
Bird, A. Perceptions of epigenetics. Nature, 2007, 447(7143), 396-398.
[http://dx.doi.org/10.1038/nature05913] [PMID: 17522671]
[71]
Jones, P.A.; Baylin, S.B. The epigenomics of cancer. Cell, 2007, 128, 683e692.
[http://dx.doi.org/10.1016/j.cell.2007.01.029]
[72]
Glasspool, R.M.; Teodoridis, J.M.; Brown, R. Epigenetics as a mechanism driving polygenic clinical drug resistance. Br. J. Cancer, 2006, 94(8), 1087-1092.
[http://dx.doi.org/10.1038/sj.bjc.6603024] [PMID: 16495912]
[73]
Senior, A.E.; al-Shawi, M.K.; Urbatsch, I.L. The catalytic cycle of P-glycoprotein. FEBS Lett., 1995, 377(3), 285-289.
[http://dx.doi.org/10.1016/0014-5793(95)01345-8] [PMID: 8549739]
[74]
Nakayama, M.; Wada, M.; Harada, T.; Nagayama, J.; Kusaba, H.; Ohshima, K.; Kozuru, M.; Komatsu, H.; Ueda, R.; Kuwano, M. Hypomethylation status of CpG sites at the promoter region and overexpression of the human MDR1 gene in acute myeloid leukemias. Blood, 1998, 92(11), 4296-4307.
[http://dx.doi.org/10.1182/blood.V92.11.4296] [PMID: 9834236]
[75]
Abolhoda, A.; Wilson, A.E.; Ross, H.; Danenberg, P.V.; Burt, M.; Scotto, K.W. Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin. Cancer Res., 1999, 5(11), 3352-3356.
[PMID: 10589744]
[76]
Pajic, M.; Iyer, J.K.; Kersbergen, A.; van der Burg, E.; Nygren, A.O.; Jonkers, J.; Borst, P.; Rottenberg, S. Moderate increase in Mdr1a/1b expression causes in vivo resistance to doxorubicin in a mouse model for hereditary breast cancer. Cancer Res., 2009, 69(16), 6396-6404.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-0041] [PMID: 19654309]
[77]
Bram, E.E.; Stark, M.; Raz, S.; Assaraf, Y.G. Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance. Neoplasia, 2009, 11(12), 1359-1370.
[http://dx.doi.org/10.1593/neo.91314] [PMID: 20019844]
[78]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[79]
Gerson, S.L. MGMT: Its role in cancer aetiology and cancer therapeutics. Nat. Rev. Cancer, 2004, 4(4), 296-307.
[http://dx.doi.org/10.1038/nrc1319] [PMID: 15057289]
[80]
Esteller, M.; Hamilton, S.R.; Burger, P.C.; Baylin, S.B.; Herman, J.G. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res., 1999, 59(4), 793-797.
[PMID: 10029064]
[81]
Esteller, M.; Garcia-Foncillas, J.; Andion, E.; Goodman, S.N.; Hidalgo, O.F.; Vanaclocha, V.; Baylin, S.B.; Herman, J.G. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N. Engl. J. Med., 2000, 343(19), 1350-1354.
[http://dx.doi.org/10.1056/NEJM200011093431901] [PMID: 11070098]
[82]
Chen, C.C.; Taniguchi, T.; D’Andrea, A. The Fanconi Anemia (FA) pathway confers glioma resistance to DNA alkylating agents. J. Mol. Med. (Berl.), 2007, 85(5), 497-509.
[http://dx.doi.org/10.1007/s00109-006-0153-2] [PMID: 17221219]
[83]
Taniguchi, T.; Tischkowitz, M.; Ameziane, N.; Hodgson, S.V.; Mathew, C.G.; Joenje, H.; Mok, S.C.; D’Andrea, A.D. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat. Med., 2003, 9(5), 568-574.
[http://dx.doi.org/10.1038/nm852] [PMID: 12692539]
[84]
Papouli, E.; Cejka, P.; Jiricny, J. Dependence of the cytotoxicity of DNA-damaging agents on the mismatch repair status of human cells. Cancer Res., 2004, 64(10), 3391-3394.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0513] [PMID: 15150090]
[85]
Strathdee, G.; MacKean, M.J.; Illand, M.; Brown, R. A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancer. Oncogene, 1999, 18(14), 2335-2341.
[http://dx.doi.org/10.1038/sj.onc.1202540] [PMID: 10327053]
[86]
Lee, S.D.; Yu, D.; Lee, D.Y.; Shin, H.S.; Jo, J.H.; Lee, Y.C. Upregulated microRNA-193a-3p is responsible for cisplatin resistance in CD44(+) gastric cancer cells. Cancer Sci., 2019, 110(2), 662-673.
[http://dx.doi.org/10.1111/cas.13894] [PMID: 30485589]
[87]
Deshmukh, A.; Binju, M.; Arfuso, F.; Newsholme, P.; Dharmarajan, A. Role of epigenetic modulation in cancer stem cell fate. Int. J. Biochem. Cell Biol., 2017, 90, 9-16.
[http://dx.doi.org/10.1016/j.biocel.2017.07.003] [PMID: 28711634]
[88]
Wapenaar, H.; Dekker, F.J. Histone acetyltransferases: Challenges in targeting bi-substrate enzymes. Clin. Epigenetics, 2016, 8, 59.
[http://dx.doi.org/10.1186/s13148-016-0225-2] [PMID: 27231488]
[89]
Cacan, E.; Ali, M.W.; Boyd, N.H.; Hooks, S.B.; Greer, S.F. Inhibition of HDAC1 and DNMT1 modulate RGS10 expression and decrease ovarian cancer chemoresistance. PLoS One, 2014, 9(1)e87455
[http://dx.doi.org/10.1371/journal.pone.0087455] [PMID: 24475290]
[90]
Meads, M.B.; Gatenby, R.A.; Dalton, W.S. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat. Rev. Cancer, 2009, 9(9), 665-674.
[http://dx.doi.org/10.1038/nrc2714] [PMID: 19693095]
[91]
Hanahan, D.; Coussens, L.M. Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell, 2012, 21(3), 309-322.
[http://dx.doi.org/10.1016/j.ccr.2012.02.022] [PMID: 22439926]
[92]
Turley, S.J.; Cremasco, V.; Astarita, J.L. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat. Rev. Immunol., 2015, 15(11), 669-682.
[http://dx.doi.org/10.1038/nri3902] [PMID: 26471778]
[93]
Velaei, K.; Samadi, N.; Barazvan, B.; Soleimani Rad, J. Tumor microenvironment-mediated chemoresistance in breast cancer. Breast, 2016, 30, 92-100.
[http://dx.doi.org/10.1016/j.breast.2016.09.002] [PMID: 27668856]
[94]
Ma, S.; Pradeep, S.; Hu, W.; Zhang, D.; Coleman, R.; Sood, A. The role of tumor microenvironment in resistance to anti-angiogenic therapy. F1000 Res., 2018, 7, 326.
[http://dx.doi.org/10.12688/f1000research.11771.1] [PMID: 29560266]
[95]
Wu, T.; Dai, Y. Tumor microenvironment and therapeutic response. Cancer Lett., 2017, 387, 61-68.
[http://dx.doi.org/10.1016/j.canlet.2016.01.043] [PMID: 26845449]
[96]
Alavi, A.S.; Acevedo, L.; Min, W.; Cheresh, D.A. Chemoresistance of endothelial cells induced by basic fibroblast growth factor depends on Raf-1-mediated inhibition of the proapoptotic kinase, ASK1. Cancer Res., 2007, 67(6), 2766-2772.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3648] [PMID: 17363598]
[97]
Hida, K.; Maishi, N.; Sakurai, Y.; Hida, Y.; Harashima, H. Heterogeneity of tumor endothelial cells and drug delivery. Adv. Drug Deliv. Rev, 2016, 99(Pt B), 140-147.
[http://dx.doi.org/10.1016/j.addr.2015.11.008] [PMID: 26626622]
[98]
Kalluri, R.; Zeisberg, M. Fibroblasts in cancer. Nat. Rev. Cancer, 2006, 6(5), 392-401.
[http://dx.doi.org/10.1038/nrc1877] [PMID: 16572188]
[99]
Pontiggia, O.; Sampayo, R.; Raffo, D.; Motter, A.; Xu, R.; Bissell, M.J. The tumormicroenvironment modulates tamoxifen resistance in breast cancer: A rolefor soluble stromal factors and fibronectin through beta1 integrin Breast. Cancer. Res. Treat., 2012, 133, 459e71.
[100]
Straussman, R.; Morikawa, T.; Shee, K.; Barzily-Rokni, M.; Qian, Z.R.; Du, J.; Davis, A.; Mongare, M.M.; Gould, J.; Frederick, D.T.; Cooper, Z.A.; Chapman, P.B.; Solit, D.B.; Ribas, A.; Lo, R.S.; Flaherty, K.T.; Ogino, S.; Wargo, J.A.; Golub, T.R. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature, 2012, 487(7408), 500-504.
[http://dx.doi.org/10.1038/nature11183] [PMID: 22763439]
[101]
Korkaya, H.; Wicha, M.S. Cancer stem cells: Nature versus nurture. Nat. Cell Biol., 2010, 12, 419-421.
[http://dx.doi.org/10.1038/ncb0510-419]
[102]
Johansson, A.C.; Ansell, A.; Jerhammar, F.; Lindh, M.B.; Grénman, R.; Munck-Wikland, E.; Östman, A.; Roberg, K. Cancer-associated fibroblasts induce matrix metalloproteinase-mediated cetuximab resistance in head and neck squamous cell carcinoma cells. Mol. Cancer Res., 2012, 10(9), 1158-1168.
[http://dx.doi.org/10.1158/1541-7786.MCR-12-0030] [PMID: 22809838]
[103]
Müerköster, S.; Wegehenkel, K.; Arlt, A.; Witt, M.; Sipos, B.; Kruse, M.L.; Sebens, T.; Klöppel, G.; Kalthoff, H.; Fölsch, U.R.; Schäfer, H. Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-1beta. Cancer Res., 2004, 64(4), 1331-1337.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-1860] [PMID: 14973050]
[104]
Wang, W.; Li, Q.; Yamada, T.; Matsumoto, K.; Matsumoto, I.; Oda, M.; Watanabe, G.; Kayano, Y.; Nishioka, Y.; Sone, S.; Yano, S. Crosstalk to stromal fibroblasts induces resistance of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors. Clin. Cancer Res., 2009, 15(21), 6630-6638.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1001] [PMID: 19843665]
[105]
Raggi, C.; Mousa, H.S.; Correnti, M.; Sica, A.; Invernizzi, P. Cancer stem cells and tumor-associated macrophages: A roadmap for multitargeting strategies. Oncogene, 2016, 35(6), 671-682.
[http://dx.doi.org/10.1038/onc.2015.132] [PMID: 25961921]
[106]
Shree, T.; Olson, O.C.; Elie, B.T.; Kester, J.C.; Garfall, A.L.; Simpson, K.; Bell-McGuinn, K.M.; Zabor, E.C.; Brogi, E.; Joyce, J.A. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev., 2011, 25(23), 2465-2479.
[http://dx.doi.org/10.1101/gad.180331.111] [PMID: 22156207]
[107]
Weizman, N.; Krelin, Y.; Shabtay-Orbach, A.; Amit, M.; Binenbaum, Y.; Wong, R.J.; Gil, Z. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene, 2014, 33(29), 3812-3819.
[http://dx.doi.org/10.1038/onc.2013.357] [PMID: 23995783]
[108]
Houthuijzen, J.M.; Daenen, L.G.; Roodhart, J.M.; Oosterom, I.; van Jaarsveld, M.T.; Govaert, K.M.; Smith, M.E.; Sadatmand, S.J.; Rosing, H.; Kruse, F.; Helms, B.J.; van Rooijen, N.; Beijnen, J.H.; Haribabu, B.; van de Lest, C.H.; Voest, E.E. Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response. Nat. Commun., 2014, 5, 5275.
[http://dx.doi.org/10.1038/ncomms6275] [PMID: 25387467]
[109]
Qian, B.Z.; Pollard, J.W. Macrophage diversity enhances tumor progression and metastasis. Cell, 2010, 141(1), 39-51.
[http://dx.doi.org/10.1016/j.cell.2010.03.014] [PMID: 20371344]
[110]
Affara, N.I.; Ruffell, B.; Medler, T.R.; Gunderson, A.J.; Johansson, M.; Bornstein, S.; Bergsland, E.; Steinhoff, M.; Li, Y.; Gong, Q.; Ma, Y.; Wiesen, J.F.; Wong, M.H.; Kulesz-Martin, M.; Irving, B.; Coussens, L.M. B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas. Cancer Cell, 2014, 25(6), 809-821.
[http://dx.doi.org/10.1016/j.ccr.2014.04.026] [PMID: 24909985]
[111]
Smith, M.P.; Sanchez-Laorden, B.; O’Brien, K.; Brunton, H.; Ferguson, J.; Young, H.; Dhomen, N.; Flaherty, K.T.; Frederick, D.T.; Cooper, Z.A.; Wargo, J.A.; Marais, R.; Wellbrock, C. The immune microenvironment confers resistance to MAPK pathway inhibitors through macrophage-derived TNFα. Cancer Discov., 2014, 4(10), 1214-1229.
[http://dx.doi.org/10.1158/2159-8290.CD-13-1007] [PMID: 25256614]
[112]
Burger, J.A.; Tsukada, N.; Burger, M.; Zvaifler, N.J.; Dell’Aquila, M.; Kipps, T.J. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood, 2000, 96(8), 2655-2663.
[http://dx.doi.org/10.1182/blood.V96.8.2655] [PMID: 11023495]
[113]
Chen, Y.; Jacamo, R.; Konopleva, M.; Garzon, R.; Croce, C.; Andreeff, M. CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia. J. Clin. Invest., 2013, 123(6), 2395-2407.
[http://dx.doi.org/10.1172/JCI66553] [PMID: 23676502]
[114]
Margolin, D.A.; Silinsky, J.; Grimes, C.; Spencer, N.; Aycock, M.; Green, H.; Cordova, J.; Davis, N.K.; Driscoll, T.; Li, L. Lymph node stromal cells enhance drug-resistant colon cancer cell tumor formation through SDF-1α/CXCR4 paracrine signaling. Neoplasia, 2011, 13(9), 874-886.
[http://dx.doi.org/10.1593/neo.11324] [PMID: 21969820]
[115]
Qiang, Y.W.; Kopantzev, E.; Rudikoff, S. Insulinlike growth factor-I signaling in multiple myeloma: Downstream elements, functional correlates, and pathway cross-talk. Blood, 2002, 99(11), 4138-4146.
[http://dx.doi.org/10.1182/blood.V99.11.4138] [PMID: 12010818]
[116]
Podar, K.; Tai, Y.T.; Davies, F.E.; Lentzsch, S.; Sattler, M.; Hideshima, T.; Lin, B.K.; Gupta, D.; Shima, Y.; Chauhan, D.; Mitsiades, C.; Raje, N.; Richardson, P.; Anderson, K.C. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood, 2001, 98(2), 428-435.
[http://dx.doi.org/10.1182/blood.V98.2.428] [PMID: 11435313]
[117]
Ogata, A.; Chauhan, D.; Teoh, G.; Treon, S.P.; Urashima, M.; Schlossman, R.L.; Anderson, K.C. IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. J. Immunol., 1997, 159(5), 2212-2221.
[PMID: 9278309]
[118]
Bourguignon, L.Y.W. Matrix hyaluronan-CD44 interaction activates MicroRNA and LncRNA signaling associated with chemoresistance, invasion, and tumor progression. Front. Oncol., 2019, 9, 492.
[http://dx.doi.org/10.3389/fonc.2019.00492] [PMID: 31293964]
[119]
Lovitt, C.J.; Shelper, T.B.; Avery, V.M. Doxorubicin resistance in breast cancer cells is mediated by extracellular matrix proteins. BMC Cancer, 2018, 18(1), 41.
[http://dx.doi.org/10.1186/s12885-017-3953-6] [PMID: 29304770]
[120]
O’Neill, C.P.; Gilligan, K.E.; Dwyer, R.M. Role of Extracellular Vesicles (EVs) in cell stress response and resistance to cancer therapy. Cancers (Basel), 2019, 11(2)E136
[http://dx.doi.org/10.3390/cancers11020136] [PMID: 30682793]
[121]
Patel, G.K.; Khan, M.A.; Bhardwaj, A.; Srivastava, S.K.; Zubair, H.; Patton, M.C.; Singh, S.; Khushman, M.; Singh, A.P. Exosomes confer chemoresistance to pancreatic cancer cells by promoting ROS detoxification and miR-155-mediated suppression of key gemcitabine-metabolising enzyme, DCK. Br. J. Cancer, 2017, 116(5), 609-619.
[http://dx.doi.org/10.1038/bjc.2017.18] [PMID: 28152544]
[122]
Corcoran, C.; Rani, S.; O’Brien, K.; O’Neill, A.; Prencipe, M.; Sheikh, R.; Webb, G.; McDermott, R.; Watson, W.; Crown, J.; O’Driscoll, L. Docetaxel-resistance in prostate cancer: Evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One, 2012, 7(12)e50999
[http://dx.doi.org/10.1371/journal.pone.0050999] [PMID: 23251413]
[123]
Ozawa, P.M.M.; Alkhilaiwi, F.; Cavalli, I.J.; Malheiros, D.; de Souza Fonseca Ribeiro, E.M.; Cavalli, L.R. Extracellular vesicles from triple-negative breast cancer cells promote proliferation and drug resistance in non-tumorigenic breast cells. Breast Cancer Res. Treat., 2018, 172(3), 713-723.
[http://dx.doi.org/10.1007/s10549-018-4925-5] [PMID: 30173296]
[124]
Cesi, G.; Philippidou, D.; Kozar, I.; Kim, Y.J.; Bernardin, F.; Van Niel, G.; Wienecke-Baldacchino, A.; Felten, P.; Letellier, E.; Dengler, S.; Nashan, D.; Haan, C.; Kreis, S. A new ALK isoform transported by extracellular vesicles confers drug resistance to melanoma cells. Mol. Cancer, 2018, 17(1), 145.
[http://dx.doi.org/10.1186/s12943-018-0886-x] [PMID: 30290811]
[125]
Wu, H.; Zeng, C.; Ye, Y.; Liu, J.; Mu, Z.; Xie, Y.; Chen, B.; Nong, Q.; Wu, D. Exosomes from irradiated nonsmall cell lung cancer cells reduced sensitivity of recipient cells to anaplastic lymphoma kinase inhibitors. Mol. Pharm., 2018, 15(5), 1892-1900.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00059] [PMID: 29595984]
[126]
Yang, J.; Weinberg, R.A. Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev. Cell, 2008, 14(6), 818-829.
[http://dx.doi.org/10.1016/j.devcel.2008.05.009] [PMID: 18539112]
[127]
Thiery, J.P.; Acloque, H.; Huang, R.Y.; Nieto, M.A. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5), 871-890.
[http://dx.doi.org/10.1016/j.cell.2009.11.007] [PMID: 19945376]
[128]
Song, Y.; Ye, M.; Zhou, J.; Wang, Z.; Zhu, X. Targeting E-cadherin expression with small molecules for digestive cancer treatment. Am. J. Transl. Res., 2019, 11(7), 3932-3944.
[PMID: 31396310]
[129]
Wang, Z.; Tang, Z.Y.; Yin, Z.; Wei, Y.B.; Liu, L.F.; Yan, B.; Zhou, K.Q.; Nian, Y.Q.; Gao, Y.L.; Yang, J.R. Metadherin regulates epithelial-mesenchymal transition in carcinoma. OncoTargets Ther., 2016, 9, 2429-2436.
[PMID: 27143938]
[130]
Liu, X.; Wang, D.; Liu, H.; Feng, Y.; Zhu, T.; Zhang, L.; Zhu, B.; Zhang, Y. Knockdown of Astrocyte Elevated Gene-1 (AEG-1) in cervical cancer cells decreases their invasiveness, epithelial to mesenchymal transition, and chemoresistance. Cell Cycle, 2014, 13(11), 1702-1707.
[http://dx.doi.org/10.4161/cc.28607] [PMID: 24675891]
[131]
Ward, A.; Balwierz, A.; Zhang, J.D.; Küblbeck, M.; Pawitan, Y.; Hielscher, T.; Wiemann, S.; Sahin, Ö. Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer. Oncogene, 2013, 32(9), 1173-1182.
[http://dx.doi.org/10.1038/onc.2012.128] [PMID: 22508479]
[132]
Smigiel, J.M.; Parameswaran, N.; Jackson, M.W. Targeting pancreatic cancer cell plasticity: The latest in therapeutics. Cancers (Basel), 2018, 10(1), 10.
[http://dx.doi.org/10.3390/cancers10010014] [PMID: 29320425]
[133]
Nieto, M.A.; Huang, R.Y.; Jackson, R.A. Thiery. J.P. EMT: Cell, 2016, 166, 21-45.
[134]
Kaur, G.; Sharma, P.; Dogra, N.; Singh, S. Eradicating cancer stem cells: Concepts, issues, and challenges. Curr. Treat. Options Oncol., 2018, 19(4), 20.
[http://dx.doi.org/10.1007/s11864-018-0533-1] [PMID: 29556842]
[135]
Cai, Z.; Cao, Y.; Luo, Y.; Hu, H.; Ling, H. Signalling mechanism(s) of epithelial-mesenchymal transition and cancer stem cells in tumour therapeutic resistance. Clin. Chim. Acta, 2018, 483, 156-163.
[http://dx.doi.org/10.1016/j.cca.2018.04.033] [PMID: 29709449]
[136]
Smith, A.L.; Robin, T.P.; Ford, H.L. Molecular pathways: Targeting the TGF-β pathway for cancer therapy. Clin. Cancer Res., 2012, 18(17), 4514-4521.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3224] [PMID: 22711703]
[137]
Wong, A.L.A.; Hirpara, J.L.; Pervaiz, S.; Eu, J.Q.; Sethi, G.; Goh B.C., Do STAT3 inhibitors have potential in the future for cancer therapy? Expert Opin. Investig. Drugs, 2017, 26(8), 883-887.
[http://dx.doi.org/10.1080/13543784.2017.1351941] [PMID: 28714740]
[138]
Dittmer, J.; Rody, A. Cancer stem cells in breast cancer. Histol. Histopathol., 2013, 28(7), 827-838.
[PMID: 23468411]
[139]
Annibaldi, A.; Widmann, C. Glucose metabolism in cancer cells. Curr. Opin. Clin. Nutr. Metab. Care, 2010, 13(4), 466-470.
[http://dx.doi.org/10.1097/MCO.0b013e32833a5577] [PMID: 20473153]
[140]
Krasnov, G.S.; Dmitriev, A.A.; Snezhkina, A.V.; Kudryavtseva, A.V. Deregulation of glycolysis in cancer: Glyceraldehyde-3-phosphate dehydrogenase as a therapeutic target. Expert Opin. Ther. Targets, 2013, 17(6), 681-693.
[http://dx.doi.org/10.1517/14728222.2013.775253] [PMID: 23445303]
[141]
Ceradini, D.J.; Kulkarni, A.R.; Callaghan, M.J.; Tepper, O.M.; Bastidas, N.; Kleinman, M.E.; Capla, J.M.; Galiano, R.D.; Levine, J.P.; Gurtner, G.C. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat. Med., 2004, 10(8), 858-864.
[http://dx.doi.org/10.1038/nm1075] [PMID: 15235597]
[142]
Sancho, P.; Burgos-Ramos, E.; Tavera, A.; Bou Kheir, T.; Jagust, P.; Schoenhals, M.; Barneda, D.; Sellers, K.; Campos-Olivas, R.; Graña, O.; Viera, C.R.; Yuneva, M.; Sainz, B., Jr; Heeschen, C. MYC/PGC-1α balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells. Cell Metab., 2015, 22(4), 590-605.
[http://dx.doi.org/10.1016/j.cmet.2015.08.015] [PMID: 26365176]
[143]
Mayer, M.J.; Klotz, L.H.; Venkateswaran, V. Metformin and prostate cancer stem cells: a novel therapeutic target. Prostate Cancer Prostatic Dis., 2015, 18(4), 303-309.
[http://dx.doi.org/10.1038/pcan.2015.35] [PMID: 26215782]
[144]
Jung, J.W.; Park, S.B.; Lee, S.J.; Seo, M.S.; Trosko, J.E.; Kang, K.S. Metformin represses self-renewal of the human breast carcinoma stem cells via inhibition of estrogen receptor-mediated OCT4 expression. PLoS One, 2011, 6(11)e28068
[http://dx.doi.org/10.1371/journal.pone.0028068] [PMID: 22132214]
[145]
Vazquez-Martin, A.; Oliveras-Ferraros, C.; Cufí, S.; Del Barco, S.; Martin-Castillo, B.; Menendez, J.A. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the Epithelial-Mesenchymal Transition (EMT) status. Cell Cycle, 2010, 9(18), 3807-3814.
[http://dx.doi.org/10.4161/cc.9.18.13131] [PMID: 20890129]
[146]
Shen, Y.A.; Lin, C.H.; Chi, W.H.; Wang, C.Y.; Hsieh, Y.T.; Wei, Y.H.; Chen, Y.J. Resveratrol impedes the stemness, epithelial-mesenchymal transition, and metabolic reprogramming of cancer stem cells in nasopharyngeal carcinoma through p53 activation. Evid. Based Complement. Alternat. Med., 2013, 2013590393
[http://dx.doi.org/10.1155/2013/590393] [PMID: 23737838]
[147]
Housman, G.; Byler, S.; Heerboth, S.; Lapinska, K.; Longacre, M.; Snyder, N.; Sarkar, S. Drug resistance in cancer: An overview. Cancers (Basel), 2014, 6(3), 1769-1792.
[http://dx.doi.org/10.3390/cancers6031769] [PMID: 25198391]
[148]
Sarkar, S.; Abujamra, A.L.; Loew, J.E.; Forman, L.W.; Perrine, S.P.; Faller, D.V. Histone deacetylase inhibitors reverse CpG methylation by regulating DNMT1 through ERK signaling. Anticancer Res., 2011, 31(9), 2723-2732.
[PMID: 21868513]
[149]
Mataga, M.A.; Rosenthal, S.; Heerboth, S.; Devalapalli, A.; Kokolus, S.; Evans, L.R.; Longacre, M.; Housman, G.; Sarkar, S. Anti-breast cancer effects of histone deacetylase inhibitors and calpain inhibitor. Anticancer Res., 2012, 32(7), 2523-2529.
[PMID: 22753709]
[150]
Sarkar, S.; Goldgar, S.; Byler, S.; Rosenthal, S.; Heerboth, S. Demethylation and re-expression of epigenetically silenced tumor suppressor genes: Sensitization of cancer cells by combination therapy. Epigenomics, 2013, 5(1), 87-94.
[http://dx.doi.org/10.2217/epi.12.68] [PMID: 23414323]
[151]
Juergens, R.A.; Wrangle, J.; Vendetti, F.P.; Murphy, S.C.; Zhao, M.; Coleman, B.; Sebree, R.; Rodgers, K.; Hooker, C.M.; Franco, N.; Lee, B.; Tsai, S.; Delgado, I.E.; Rudek, M.A.; Belinsky, S.A.; Herman, J.G.; Baylin, S.B.; Brock, M.V.; Rudin, C.M. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov., 2011, 1(7), 598-607.
[http://dx.doi.org/10.1158/2159-8290.CD-11-0214] [PMID: 22586682]
[152]
Zhu, Y.; Yu, F.; Tan, Y.; Yuan, H.; Hu, F. Strategies of targeting pathological stroma for enhanced antitumor therapies. Pharmacol. Res., 2019, 148104401
[http://dx.doi.org/10.1016/j.phrs.2019.104401] [PMID: 31422113]
[153]
Thakkar, S.; Sharma, D.; Kalia, K.; Tekade, R.K. Tumor microenvironment targeted nanotherapeutics for cancer therapy and diagnosis: A review. Acta Biomater., 2020, 101, 43-68.
[154]
Gurpinar, E.; Grizzle, W.E.; Piazza, G.A. NSAIDs inhibit tumorigenesis, but how? Clin. Cancer Res., 2014, 20(5), 1104-1113.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-1573] [PMID: 24311630]
[155]
Blidner, A.G.; Salatino, M.; Mascanfroni, I.D.; Diament, M.J.; Bal de Kier Joffé, E.; Jasnis, M.A.; Klein, S.M.; Rabinovich, G.A. Differential response of myeloid-derived suppressor cells to the nonsteroidal anti-inflammatory agent indomethacin in tumor-associated and tumor-free microenvironments. J. Immunol., 2015, 194(7), 3452-3462.
[http://dx.doi.org/10.4049/jimmunol.1401144] [PMID: 25740944]
[156]
Deep, G.; Agarwal, R. Targeting tumor microenvironment with silibinin: promise and potential for a translational cancer chemopreventive strategy. Curr. Cancer Drug Targets, 2013, 13(5), 486-499.
[http://dx.doi.org/10.2174/15680096113139990041] [PMID: 23617249]
[157]
Jahchan, N.S.; Mujal, A.M.; Pollack, J.L.; Binnewies, M.; Sriram, V.; Reyno, L.; Krummel, M.F. Tuning the tumor myeloid microenvironment to fight cancer. Front. Immunol., 2019, 10, 1611.
[http://dx.doi.org/10.3389/fimmu.2019.01611] [PMID: 31402908]
[158]
Paolicchi, E.; Gemignani, F.; Krstic-Demonacos, M.; Dedhar, S.; Mutti, L.; Landi, S. Targeting hypoxic response for cancer therapy. Oncotarget, 2016, 7(12), 13464-13478.
[http://dx.doi.org/10.18632/oncotarget.7229] [PMID: 26859576]
[159]
Yu, T.; Tang, B.; Sun, X. Development of inhibitors targeting hypoxia-inducible factor 1 and 2 for cancer therapy. Yonsei Med. J., 2017, 58(3), 489-496.
[http://dx.doi.org/10.3349/ymj.2017.58.3.489] [PMID: 28332352]
[160]
Duffy, A.G.; Melillo, G.; Turkbey, B.; Allen, D.; Choyke, P.L.; Chen, C.; Raffeld, M.; Doroshow, J.H.; Murgo, A.; Kummar, S. A pilot trial of oral topotecan (TPT) in patients with refractory advanced solid neoplasms expressing HIF-1α. J. Clin. Oncol., 2010, 28e13518
[http://dx.doi.org/10.1200/jco.2010.28.15_suppl.e13518]
[161]
Yuan, J.; Wu, Y.; Lu, G. α-Mangostin suppresses lipopolysaccharide-induced invasion by inhibiting matrix metalloproteinase-2/9 and increasing E-cadherin expression through extracellular signal-regulated kinase signaling in pancreatic cancer cells. Oncol. Lett., 2013, 5(6), 1958-1964.
[http://dx.doi.org/10.3892/ol.2013.1290] [PMID: 23833675]
[162]
Zhu, Y.; Liu, Y.; Qian, Y.; Dai, X.; Yang, L.; Chen, J.; Guo, S.; Hisamitsu, T. Research on the efficacy of Celastrus orbiculatus in suppressing TGF-β1-induced epithelial-mesenchymal transition by inhibiting HSP27 and TNF-α-induced NF-κB/Snail signaling pathway in human gastric adenocarcinoma. BMC Complement. Altern. Med., 2014, 14, 433.
[http://dx.doi.org/10.1186/1472-6882-14-433] [PMID: 25370696]
[163]
Han, Y.H.; Kee, J.Y.; Kim, D.S.; Mun, J.G.; Jeong, M.Y.; Park, S.H.; Choi, B.M.; Park, S.J.; Kim, H.J.; Um, J.Y.; Hong, S.H. Arctigenin inhibits lung metastasis of colorectal cancer by regulating cell viability and metastatic phenotypes. Molecules, 2016, 21(9), 21.
[http://dx.doi.org/10.3390/molecules21091135] [PMID: 27618887]
[164]
Li, W.; Zhai, L.; Zhao, C.; Lv, S. MiR-153 inhibits epithelial-mesenchymal transition by targeting metadherin in human breast cancer. Breast Cancer Res. Treat., 2015, 150(3), 501-509.
[http://dx.doi.org/10.1007/s10549-015-3346-y] [PMID: 25794773]
[165]
Wang, L.; Liu, Z.; Ma, D.; Piao, Y.; Guo, F.; Han, Y.; Xie, X. SU6668 suppresses proliferation of triple negative breast cancer cells through down-regulating MTDH expression. Cancer Cell Int., 2013, 13(1), 88.
[http://dx.doi.org/10.1186/1475-2867-13-88] [PMID: 23984913]