Stem Cells: Therapeutic Implications in Chemotherapy and Radiotherapy
Resistance in Cancer Therapy

Tejaswini      Patil; Sonali   S.   Rohiwal; Arpita   P.   Tiwari
doi:10.2174/1574888X17666221003125208
Abstract

Cancer stem cells (CSCs) are transformed forms of normal stem cells within heterogeneous mixture of cancer cells. These are mainly responsible for the recurrence of cancer after treatment because of their ability to develop resistance against chemo and radiotherapy due to various factors such as activation of signalling pathways important for self-renewal, DNA repair capacity, microenvironment and expression of ABC transporters. Targeting these mechanisms as potential factors can eliminate CSCs, which eventually decreases cancer recurrence. This review focuses on the characteristics of CSCs, their role in the development of resistance to chemotherapy and radiotherapy along with the therapeutic potential targets for successful elimination of CSC population.
Keywords: Cancer Stem cells, Chemotherapy, Radiotherapy, Drug resistance, Cancer therapy
« Previous Next »
Graphical Abstract

[1]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell  2011; 144(5): 646-74.

[2]
Lathia J, Liu H, Matei D. The clinical impact of cancer stem cells. Oncologist  2020; 25(2): 123-31.
 [http://dx.doi.org/10.1634/theoncologist.2019-0517] [PMID:  32043793]

[3]
Steinbichler TB, Dudás J, Skvortsov S, Ganswindt U, Riechelmann H, Skvortsova II. Therapy resistance mediated by cancer stem cells. Semin Cancer Biol  2018; 53: 156-67.
 [http://dx.doi.org/10.1016/j.semcancer.2018.11.006]

[4]
Tiwari AP, Thorat ND, Pricl S, Patil RM, Rohiwal S, Townley H. Bioink: A 3D-bioprinting tool for anticancer drug discovery and cancer management. Drug Discov Today  2021; 26(7): 1574-90.
 [http://dx.doi.org/10.1016/j.drudis.2021.03.010] [PMID:  33741496]

[5]
Melo FDSE, Vermeulen L, Fessler E, Medema JP. Cancer heterogeneity-A multifaceted view. EMBO Rep  2013; 14(8): 686-95.
 [http://dx.doi.org/10.1038/embor.2013.92] [PMID:  23846313]

[6]
Kuşoğlu A, Biray Avcı Ç. Cancer stem cells: A brief review of the current status. Gene  2019; 681: 80-5.
 [http://dx.doi.org/10.1016/j.gene.2018.09.052] [PMID:  30268439]

[7]
Batlle E, Clevers H. Cancer stem cells revisited. Nat Med  2017; 23(10): 1124-34.
 [http://dx.doi.org/10.1038/nm.4409] [PMID:  28985214]

[8]
Haggard HW. The conception of cancer before and after Johannes Müller. Bull N Y Acad Med  1938; 14(4): 183-97.
 [PMID:  19312055]

[9]
Cooper M. Regenerative pathologies: Stem cells, teratomas and theories of cancer. Med Stud  2009; 1(1): 55-66.
 [http://dx.doi.org/10.1007/s12376-008-0002-4]

[10]
Maehle AH. Ambiguous cells: The emergence of the stem cell concept in the nineteenth and twentieth centuries. Notes Rec R Soc Lond  2011; 65(4): 359-78.
 [http://dx.doi.org/10.1098/rsnr.2011.0023] [PMID:  22332468]

[11]
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med  1997; 3(7): 730-7.
 [http://dx.doi.org/10.1038/nm0797-730] [PMID:  9212098]

[12]
Elble RC, Ramena G, Elble RC. The role of cancer stem cells in relapse of solid tumors. Front Biosci  2012; 4(4): 1528-41.
 [http://dx.doi.org/10.2741/e478] [PMID:  22201973]

[13]
Li W, Ma H, Zhang J, Zhu L, Wang C, Yang Y. Unraveling the roles of CD44/CD24 and ALDH1 as cancer stem cell markers in tumorigenesis and metastasis. Sci Rep  2017; 7(1): 13856.
 [http://dx.doi.org/10.1038/s41598-017-14364-2] [PMID:  29062075]

[14]
Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature  2004; 432(7015): 396-401.

[15]
Heng WS, Gosens R, Kruyt FAE. Lung cancer stem cells: Origin, features, maintenance mechanisms and therapeutic targeting. Biochem Pharmacol  2019; 160: 121-33.
 [http://dx.doi.org/10.1016/j.bcp.2018.12.010] [PMID:  30557553]

[16]
Garza Trevino EN, Said-Fernadez SL, Martínez-Rodriguez HG. Understanding the colon cancer stem cells and perspectives on treatment. Cancer Cell Int  2015; 15(1): 2.
 [http://dx.doi.org/10.1186/s12935-015-0163-7] [PMID:  25685060]

[17]
Parmiani G. Melanoma cancer stem cells: Markers and functions. Cancers  2016; 8(3): 34.
 [http://dx.doi.org/10.3390/cancers8030034] [PMID:  26978405]

[18]
Akbarzadeh M, Maroufi NF, Tazehkand AP, et al. Current approaches in identification and isolation of cancer stem cells. J Cell Physiol  2019; 234(9): 14759-72.
 [http://dx.doi.org/10.1002/jcp.28271] [PMID:  30741412]

[19]
Liu Y, Wang G, Zhang J, et al. CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia. Stem Cell Res Ther  2021; 12(1): 86.
 [http://dx.doi.org/10.1186/s13287-021-02155-6] [PMID:  33494824]

[20]
Latuske EM, Stamm H, Klokow M, et al. Combined inhibition of GLI and FLT3 signaling leads to effective anti-leukemic effects in human acute myeloid leukemia. Oncotarget  2017; 8(17): 29187-201.
 [http://dx.doi.org/10.18632/oncotarget.16304] [PMID:  28418873]

[21]
Yan W, Chen Y, Yao Y, Zhang H, Wang T. Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice. Cancer Cell Int  2013; 13(1): 62.
 [http://dx.doi.org/10.1186/1475-2867-13-62] [PMID:  23305405]

[22]
Das PK, Rakib MA, Khanam JA, Pillai S, Islam F. Novel therapeutics against breast cancer stem cells by targeting surface markers and signaling pathways. Curr Stem Cell Res Ther  2019; 14(8): 669-82.
 [http://dx.doi.org/10.2174/1574888X14666190628104721] [PMID:  31808385]

[23]
Prabavathy D, Swarnalatha Y, Ramadoss N. Lung cancer stem cells-origin, characteristics and therapy. Stem Cell Investig  2018; 5: 6.
 [http://dx.doi.org/10.21037/sci.2018.02.01] [PMID:  29682513]

[24]
He J, Liu Y, Zhu T, et al. CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. Mol Cell Proteomics  2012; 11(6): M111.010744.
 [http://dx.doi.org/10.1074/mcp.M111.010744] [PMID: 22203689]

[25]
Abou-Antoun TJ, Hale JS, Lathia JD, Dombrowski SM. Brain cancer stem cells in adults and children: Cell biology and therapeutic implications. Neurotherapeutics  2017; 14(2): 372-84.
 [http://dx.doi.org/10.1007/s13311-017-0524-0] [PMID:  28374184]

[26]
Lugli A, Iezzi G, Hostettler I, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer  2010; 103(3): 382-90.
 [http://dx.doi.org/10.1038/sj.bjc.6605762] [PMID:  20606680]

[27]
Sahlberg SH, Spiegelberg D, Glimelius B, Stenerlöw B, Nestor M. Evaluation of cancer stem cell markers CD133, CD44, CD24: Association with AKT isoforms and radiation resistance in colon cancer cells. PLoS One  2014; 9(4): e94621.
 [http://dx.doi.org/10.1371/journal.pone.0094621] [PMID:  24760019]

[28]
Yin Q, Shi X, Lan S, Jin H, Wu D. Effect of melanoma stem cells on melanoma metastasis. Oncol Lett  2021; 22(1): 566.
 [http://dx.doi.org/10.3892/ol.2021.12827] [PMID:  34113394]

[29]
Gzil A, Zarębska I, Bursiewicz W, Antosik P, Grzanka D, Szylberg Ł. Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Mol Biol Rep  2019; 46(6): 6629-45.
 [http://dx.doi.org/10.1007/s11033-019-05058-1] [PMID:  31486978]

[30]
Ojalill M, Parikainen M, Rappu P, et al. Integrin α2β1 decelerates proliferation, but promotes survival and invasion of prostate cancer cells. Oncotarget  2018; 9(65): 32435-47.
 [http://dx.doi.org/10.18632/oncotarget.25945] [PMID:  30197754]

[31]
Moltzahn F, Thalmann GN. Cancer stem cells in prostate cancer. Transl Androl Urol  2013; 2(3): 242-53.
 [PMID:  26816738]

[32]
Zhang R, Zhang P, Wang H, et al. Inhibitory effects of metformin at low concentration on epithelial–mesenchymal transition of CD44+CD117+ ovarian cancer stem cells. Stem Cell Res Ther  2015; 6(1): 262.
 [http://dx.doi.org/10.1186/s13287-015-0249-0] [PMID:  26718286]

[33]
Lou W, Liu J, Gao Y, et al. MicroRNA regulation of liver cancer stem cells. Am J Cancer Res  2018; 8(7): 1126-41.
 [PMID:  30094089]

[34]
Fu L, Bu L, Yasuda T, et al. Gastric cancer stem cells: Current insights into the immune microenvironment and therapeutic targets. Biomedicines  2020; 8(1): 7.
 [http://dx.doi.org/10.3390/biomedicines8010007] [PMID:  31935894]

[35]
Zhang C, Li C, He F, Cai Y, Yang H. Identification of CD44+CD24+ gastric cancer stem cells. J Cancer Res Clin Oncol  2011; 137(11): 1679-86.
 [http://dx.doi.org/10.1007/s00432-011-1038-5] [PMID:  21882047]

[36]
Ahmed EM, Bandopadhyay G, Coyle B, Grabowska A. A HIF-independent, CD133-mediated mechanism of cisplatin resistance in glioblastoma cells. Cell Oncol  2018; 41(3): 319-28.
 [http://dx.doi.org/10.1007/s13402-018-0374-8] [PMID:  29492900]

[37]
Pineda JR, Badiola I, Ibarretxe G. Stem and cancer stem cell identities, cellular markers, niche environment and response to treatments to unravel new therapeutic targets. Biology  2021; 10(1): 25.

[38]
Papaccio F, Paino F, Regad T, Papaccio G, Desiderio V, Tirino V. Concise review: Cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Transl Med  2017; 6(12): 2115-25.
 [http://dx.doi.org/10.1002/sctm.17-0138] [PMID:  29072369]

[39]
Shackleton M. Normal stem cells and cancer stem cells: Similar and different. Semin Cancer Biol  2010; 2(2): 85-92.
 [http://dx.doi.org/10.1016/j.semcancer.2010.04.002]

[40]
Walcher L, Kistenmacher AK, Suo H, et al. Cancer stem cells—Origins and biomarkers: Perspectives for targeted personalized therapies. Front Immunol  2020; 11: 1280.
 [http://dx.doi.org/10.3389/fimmu.2020.01280] [PMID:  32849491]

[41]
Friedmann Morvinski D, Verma IM. Dedifferentiation and reprogramming: Origins of cancer stem cells. EMBO Rep  2014; 15(3): 244-53.
 [http://dx.doi.org/10.1002/embr.201338254] [PMID:  24531722]

[42]
Rahman M, Jamil HM, Akhtar N, Rahman KMT, Islam R, Asaduzzaman SM. Stem cell and cancer stem cell: A tale of two cells. Prog Stem Cell  2016; 3(2): 97-108.
 [http://dx.doi.org/10.15419/psc.v3i02.124]

[43]
Najafi M, Mortezaee K, Majidpoor J. Cancer Stem Cell (CSC) resistance drivers. Life Sci  2019; 234: 116781.
 [http://dx.doi.org/10.1016/j.lfs.2019.116781] [PMID:  31430455]

[44]
Makena MR, Ranjan A, Thirumala V, Reddy AP. Cancer stem cells: Road to therapeutic resistance and strategies to overcome resistance. Biochim Biophys Acta Mol Basis Dis  2020; 1866(4): 165339.
 [http://dx.doi.org/10.1016/j.bbadis.2018.11.015] [PMID:  30481586]

[45]
Najafi M, Mortezaee K, Ahadi R. Cancer stem cell (a)symmetry & plasticity: Tumorigenesis and therapy relevance. Life Sci  2019; 231: 116520.
 [http://dx.doi.org/10.1016/j.lfs.2019.05.076] [PMID:  31158379]

[46]
Bu P, Chen KY, Lipkin SM, Shen X. Asymmetric division: A marker for cancer stem cells? Oncotarget  2013; 4(7): 950-1.
 [http://dx.doi.org/10.18632/oncotarget.1029] [PMID:  23807730]

[47]
Li Z, Zhang YY, Zhang H, Yang J, Chen Y, Lu H. Asymmetric cell division and tumor heterogeneity. Front Cell Dev Biol  2022; 10: 938685.
 [http://dx.doi.org/10.3389/fcell.2022.938685] [PMID:  35859890]

[48]
Hitomi M, Chumakova AP, Silver DJ, et al. Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells. JCI Insight  2021; 6(3): e130510.
 [http://dx.doi.org/10.1172/jci.insight.130510] [PMID:  33351787]

[49]
Barbato L, Bocchetti M, Di Biase A, Regad T. Cancer stem cells and targeting strategies. Cells  2019; 8(8): 926.
 [http://dx.doi.org/10.3390/cells8080926] [PMID:  31426611]

[50]
Zhao J. Cancer stem cells and chemoresistance: The smartest survives the raid. Pharmacol Ther  2016; 160: 145-58.
 [http://dx.doi.org/10.1016/j.pharmthera.2016.02.008] [PMID:  26899500]

[51]
Regad T. Tissue-specific cancer stem cells: Reality or a mirage? Translational Medicine Reports  2017; 1(1): 6535.

[52]
Zeijlemaker W, Grob T, Meijer R, et al. CD34+CD38− leukemic stem cell frequency to predict outcome in acute myeloid leukemia. Leukemia  2019; 33(5): 1102-12.
 [http://dx.doi.org/10.1038/s41375-018-0326-3] [PMID:  30542144]

[53]
Quintás CA, Cortes J. Molecular biology of bcr-abl1–positive chronic myeloid leukemia. Blood  2009; 113(8): 1619-30.
 [http://dx.doi.org/10.1182/blood-2008-03-144790] [PMID:  18827185]

[54]
Loscocco F, Visani G, Galimberti S, Curti A, Isidori A. BCR-ABL independent mechanisms of resistance in chronic myeloid leukemia. Front Oncol  2019; 9: 939.
 [http://dx.doi.org/10.3389/fonc.2019.00939] [PMID:  31612105]

[55]
Tanaka Y, Fukushima T, Mikami K, et al. Efficacy of tyrosine kinase inhibitors on a mouse chronic myeloid leukemia model and chronic myeloid leukemia stem cells. Exp Hematol  2020; 90: 46-51.
 [http://dx.doi.org/10.1016/j.exphem.2020.09.186] [PMID:  32910995]

[56]
Marzagalli M, Fontana F, Raimondi M, Limonta P. Cancer stem cells-key players in tumor relapse. Cancers  2021; 13(3): 376.
 [http://dx.doi.org/10.3390/cancers13030376] [PMID:  33498502]

[57]
Vikram R, Chou WC, Hung SC, Shen CY. Tumorigenic and metastatic role of CD44−/low/CD24−/low cells in luminal breast cancer. Cancers  2020; 12(5): 1239.
 [http://dx.doi.org/10.3390/cancers12051239] [PMID:  32423137]

[58]
Jang JW, Song Y, Kim SH, Kim J, Seo HR. Potential mechanisms of CD133 in cancer stem cells. Life Sci  2017; 184: 25-9.
 [http://dx.doi.org/10.1016/j.lfs.2017.07.008] [PMID:  28697984]

[59]
Li B, McCrudden CM, Yuen HF, et al. CD133 in brain tumor: The prognostic factor. Oncotarget  2017; 8(7): 11144-59.
 [http://dx.doi.org/10.18632/oncotarget.14406] [PMID:  28055976]

[60]
Zhou HM, Zhang JG, Zhang X, Li Q. Targeting cancer stem cells for reversing therapy resistance: Mechanism, signaling, and prospective agents. Signal Transduct Target Ther  2021; 6(1): 62.
 [http://dx.doi.org/10.1038/s41392-020-00430-1] [PMID:  33589595]

[61]
Begicevic RR, Falasca M. ABC transporters in cancer stem cells: Beyond chemoresistance. Int J Mol Sci  2017; 18(11): 2362.
 [http://dx.doi.org/10.3390/ijms18112362] [PMID:  29117122]

[62]
Ajani JA, Song S, Hochster HS, Steinberg IB. Cancer stem cells: The promise and the potential. Semin Oncol  2015; 42: S3-S17.
 [http://dx.doi.org/10.1053/j.seminoncol.2015.01.001]

[63]
Kolenda J, Jensen SS, Aaberg-Jessen C, et al. Effects of hypoxia on expression of a panel of stem cell and chemoresistance markers in glioblastoma-derived spheroids. J Neurooncol  2011; 103(1): 43-58.
 [http://dx.doi.org/10.1007/s11060-010-0357-8] [PMID:  20835751]

[64]
Shaffer BC, Gillet JP, Patel C, Baer MR, Bates SE, Gottesman MM. Drug resistance: Still a daunting challenge to the successful treatment of AML. Drug Resist Updat  2012; 15(1-2): 62-9.
 [http://dx.doi.org/10.1016/j.drup.2012.02.001] [PMID:  22409994]

[65]
Xi G, Hayes E, Lewis R, et al. CD133 and DNA-PK regulate MDR1 via the PI3K- or Akt-NF-κB pathway in multidrug-resistant glioblastoma cells in vitro. Oncogene  2016; 35(2): 241-50.
 [http://dx.doi.org/10.1038/onc.2015.78] [PMID:  25823028]

[66]
Waters JA, House CD. Ovarian Cancer Stem Cell Biology and Chemoresistance. In: Goli Samimi, Christina Annunziata, Eds Overcoming Ovarian Cancer Chemoresistance.  United States: Academic Press 2021; pp. 55-77.
 [http://dx.doi.org/10.1016/B978-0-12-819840-7.00009-1]

[67]
O’Conor CJ, Chen T, González I, Cao D, Peng Y. Cancer stem cells in triple-negative breast cancer: A potential target and prognostic marker. Biomarkers Med  2018; 12(7): 813-20.
 [http://dx.doi.org/10.2217/bmm-2017-0398] [PMID:  29902924]

[68]
D’Arcy MS. Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int  2019; 43(6): 582-92.
 [http://dx.doi.org/10.1002/cbin.11137] [PMID:  30958602]

[69]
Safa AR. Resistance to cell death and its modulation in cancer stem cells. Crit Rev Oncog  2016; 21(3-4): 203-19.
 [http://dx.doi.org/10.1615/CritRevOncog.2016016976]

[70]
Tao J, Qiu B, Zhang D, Wang Y. Expression levels of Fas/Fas-L mRNA in human brain glioma stem cells. Mol Med Rep  2012; 5(5): 1202-6.
 [http://dx.doi.org/10.3892/mmr.2012.791] [PMID:  22344564]

[71]
Eisele G, Wolpert F, Decrey G, Weller M. APO010, a synthetic hexameric CD95 ligand, induces death of human glioblastoma stem-like cells. Anticancer Res  2013; 33(9): 3563-71.
 [PMID:  24023281]

[72]
Lee DH, Oh SC, Giles AJ, Jung J, Gilbert MR, Park DM. Cardiac glycosides suppress the maintenance of stemness and malignancy via inhibiting HIF-1α in human glioma stem cells. Oncotarget  2017; 8(25): 40233-45.
 [http://dx.doi.org/10.18632/oncotarget.16714] [PMID:  28410215]

[73]
Yao ZG, Li WH, Hua F, et al. LBH589 inhibits glioblastoma growth and angiogenesis through suppression of HIF-1α expression. J Neuropathol Exp Neurol  2017; 76(12): 1000-7.
 [http://dx.doi.org/10.1093/jnen/nlx088] [PMID:  29136455]

[74]
Weisberg E, Azab AK, Manley PW, et al. Inhibition of CXCR4 in CML cells disrupts their interaction with the bone marrow microenvironment and sensitizes them to nilotinib. Leukemia  2012; 26(5): 985-90.
 [http://dx.doi.org/10.1038/leu.2011.360] [PMID:  22182920]

[75]
Brescia P, Ortensi B, Fornasari L, Levi D, Broggi G, Pelicci G. CD133 is essential for glioblastoma stem cell maintenance. Stem Cells  2013; 31(5): 857-69.
 [http://dx.doi.org/10.1002/stem.1317] [PMID:  23307586]

[76]
Vora P, Venugopal C, Salim SK, et al. The rational development of CD133-targeting immunotherapies for glioblastoma. Cell Stem Cell  2020; 26(6): 832-844.e6.
 [http://dx.doi.org/10.1016/j.stem.2020.04.008] [PMID:  32464096]

[77]
Thankamony AP, Saxena K, Murali R, Jolly MK, Nair R. Cancer stem cell plasticity–A deadly deal. Front Mol Biosci  2020; 7: 79.
 [http://dx.doi.org/10.3389/fmolb.2020.00079] [PMID:  32426371]

[78]
Lainez-Gonzalez D, Serrano-Lopez J, Alonso-Dominguez JM. Understanding the hedgehog signaling pathway in acute myeloid leukemia stem cells: A necessary step toward a cure. Biology  2021; 10(4): 255.
 [http://dx.doi.org/10.3390/biology10040255] [PMID:  33804919]

[79]
Zeng X, Zhao H, Li Y, et al. Targeting Hedgehog signaling pathway and autophagy overcomes drug resistance of BCR-ABL-positive chronic myeloid leukemia. Autophagy  2015; 11(2): 355-72.
 [http://dx.doi.org/10.4161/15548627.2014.994368] [PMID:  25701353]

[80]
Venkatesh V, Nataraj R, Thangaraj GS, et al. Targeting Notch signalling pathway of cancer stem cells. Stem Cell Investig  2018; 5: 5.
 [http://dx.doi.org/10.21037/sci.2018.02.02] [PMID:  29682512]

[81]
Suman S, Das TP, Damodaran C. Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells. Br J Cancer  2013; 109(10): 2587-96.
 [http://dx.doi.org/10.1038/bjc.2013.642] [PMID:  24129237]

[82]
Fan X, Khaki L, Zhu TS, et al. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells  2010; 28(1): 5-16.
 [http://dx.doi.org/10.1002/stem.254] [PMID:  19904829]

[83]
Liu J, Pan S, Hsieh MH, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA  2013; 110(50): 20224-9.
 [http://dx.doi.org/10.1073/pnas.1314239110] [PMID:  24277854]

[84]
Heidel FH, Bullinger L, Feng Z, et al. Genetic and pharmacologic inhibition of β-catenin targets imatinib-resistant leukemia stem cells in CML. Cell Stem Cell  2012; 10(4): 412-24.
 [http://dx.doi.org/10.1016/j.stem.2012.02.017] [PMID:  22482506]

[85]
Yoon S, Eom GH. HDAC and HDAC inhibitor: From cancer to cardiovascular diseases. Chonnam Med J  2016; 52(1): 1-11.
 [http://dx.doi.org/10.4068/cmj.2016.52.1.1] [PMID:  26865995]

[86]
Dong C, Yuan T, Wu Y, et al. Loss of FBP1 by snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer Cell  2013; 23(3): 316-31.
 [http://dx.doi.org/10.1016/j.ccr.2013.01.022] [PMID:  23453623]

[87]
Lin J, Lee JHJ, Paramasivam K, et al. Induced-decay of glycine decarboxylase transcripts as an anticancer therapeutic strategy for non-small-cell lung carcinoma. Mol Ther Nucleic Acids  2017; 9: 263-73.
 [http://dx.doi.org/10.1016/j.omtn.2017.10.001] [PMID:  29246305]

[88]
Bartucci M, Svensson S, Romania P, et al. Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy. Cell Death Differ  2012; 19(5): 768-78.
 [http://dx.doi.org/10.1038/cdd.2011.170] [PMID:  22117197]

[89]
Byers LA, Navarro A, Schaefer E, et al. A phase II trial of prexasertib (LY2606368) in patients with extensive-stage small-cell lung cancer. Clin Lung Cancer  2021; 22(6): 531-40.
 [http://dx.doi.org/10.1016/j.cllc.2021.04.005] [PMID:  34034991]

[90]
Liu Y, Burness ML, Martin-Trevino R, et al. RAD51 mediates resistance of cancer stem cells to PARP inhibition in triple-negative breast cancer. Clin Cancer Res  2017; 23(2): 514-22.
 [http://dx.doi.org/10.1158/1078-0432.CCR-15-1348] [PMID:  28034904]

[91]
Shkundina IS, Gall AA, Dick A, Cocklin S, Mazin AV. New RAD51 inhibitors to target homologous recombination in human cells. Genes  2021; 12(6): 920.
 [http://dx.doi.org/10.3390/genes12060920] [PMID:  34208492]

[92]
Vey N, Delaunay J, Martinelli G, et al. Phase I clinical study of RG7356, an anti-CD44 humanized antibody, in patients with acute myeloid leukemia. Oncotarget  2016; 7(22): 32532-42.
 [http://dx.doi.org/10.18632/oncotarget.8687] [PMID:  27081038]

[93]
Sikic BI, Lakhani N, Patnaik A, et al. First-in-human, first-in-class phase I trial of the anti-CD47 antibody Hu5F9-G4 in patients with advanced cancers. J Clin Oncol  2019; 37(12): 946-53.
 [http://dx.doi.org/10.1200/JCO.18.02018] [PMID:  30811285]

[94]
Liu X, Kwon H, Li Z, Fu Y. Is CD47 an innate immune checkpoint for tumor evasion? J Hematol Oncol  2017; 10(1): 12.
 [http://dx.doi.org/10.1186/s13045-016-0381-z] [PMID:  28077173]

[95]
Advani R, Flinn I, Popplewell L, et al. CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin’s lymphoma. N Engl J Med  2018; 379(18): 1711-21.
 [http://dx.doi.org/10.1056/NEJMoa1807315]

[96]
Nandi A, Chakrabarti R. The many facets of Notch signaling in breast cancer: Toward overcoming therapeutic resistance. Genes Dev  2020; 34(21-22): 1422-38.
 [http://dx.doi.org/10.1101/gad.342287.120] [PMID:  33872192]

[97]
Van Vlerken LE, Hurt EM, Hollingsworth RE. The role of epigenetic regulation in stem cell and cancer biology. J Mol Med (Berl)  2012; 90(7): 791-801.
 [http://dx.doi.org/10.1007/s00109-012-0917-9] [PMID:  22660276]

[98]
Zhang WC, Shyh-Chang N, Yang H, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell  2012; 148(1-2): 259-72.
 [http://dx.doi.org/10.1016/j.cell.2011.11.050] [PMID:  22225612]

[99]
Atun R, Jaffray DA, Barton MB, et al. Expanding global access to radiotherapy. Lancet Oncol  2015; 16(10): 1153-86.
 [http://dx.doi.org/10.1016/S1470-2045(15)00222-3] [PMID:  26419354]

[100]
Arnold CR, Mangesius J, Skvortsova II, Ganswindt U. The role of cancer stem cells in radiation resistance. Front Oncol  2020; 10: 164.
 [http://dx.doi.org/10.3389/fonc.2020.00164] [PMID:  32154167]

[101]
Mladenov E, Magin S, Soni A, Iliakis G. DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: Cell cycle and proliferation-dependent regulation. Semin Cancer Biol  2016; 37: 51-64.

[102]
Morgan MA, Lawrence TS. Molecular pathways: Overcoming radiation resistance by targeting DNA damage response pathways. Clin Cancer Res  2015; 21(13): 2898-904.
 [http://dx.doi.org/10.1158/1078-0432.CCR-13-3229] [PMID:  26133775]

[103]
Peitzsch C, Tyutyunnykova A, Pantel K, Dubrovska A. Cancer stem cells: The root of tumor recurrence and metastases. Semin Cancer Biol  2017; 44: 10-24.
 [http://dx.doi.org/10.1016/j.semcancer.2017.02.011]

[104]
Chen Y, Li D, Wang D, et al. Quiescence and attenuated DNA damage response promote survival of esophageal cancer stem cells. J Cell Biochem  2012; 113(12): 3643-52.
 [http://dx.doi.org/10.1002/jcb.24228] [PMID:  22711554]

[105]
Karanam K, Kafri R, Loewer A, Lahav G. Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and a maximal use of HR in mid S phase. Mol Cell  2012; 47(2): 320-9.
 [http://dx.doi.org/10.1016/j.molcel.2012.05.052] [PMID:  22841003]

[106]
Krause M, Dubrovska A, Linge A, Baumann M. Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv Rev  2017; 109: 63-73.
 [http://dx.doi.org/10.1016/j.addr.2016.02.002] [PMID:  26877102]

[107]
Chang L, Graham P, Hao J, et al. Cancer stem cells and signaling pathways in radioresistance. Oncotarget  2016; 7(10): 11002-17.
 [http://dx.doi.org/10.18632/oncotarget.6760] [PMID:  26716904]

[108]
Peitzsch C, Perrin R, Hill RP, Dubrovska A, Kurth I. Hypoxia as a biomarker for radioresistant cancer stem cells. Int J Radiat Biol  2014; 90(8): 636-52.
 [http://dx.doi.org/10.3109/09553002.2014.916841] [PMID:  24844374]

[109]
Peitzsch C, Kurth I, Kunz-Schughart L, Baumann M, Dubrovska A. Discovery of the cancer stem cell related determinants of radioresistance. Radiother Oncol  2013; 108(3): 378-87.
 [http://dx.doi.org/10.1016/j.radonc.2013.06.003] [PMID:  23830195]

[110]
Schulz A, Meyer F, Dubrovska A, Borgmann K. Cancer stem cells and radioresistance: DNA repair and beyond. Cancers  2019; 11(6): 862.
 [http://dx.doi.org/10.3390/cancers11060862] [PMID:  31234336]

[111]
Qin J, Liu Y, Lu Y, et al. Hypoxia-inducible factor 1 alpha promotes cancer stem cells-like properties in human ovarian cancer cells by upregulating SIRT1 expression. Sci Rep  2017; 7(1): 10592.
 [http://dx.doi.org/10.1038/s41598-017-09244-8] [PMID:  28878214]

[112]
Luo M, Wicha MS. Targeting cancer stem cell redox metabolism to enhance therapy responses. Semin Radiat Oncol  2019; 29(1): 42-54.
 [http://dx.doi.org/10.1016/j.semradonc.2018.10.003]

[113]
Plaks V, Kong N, Werb Z. The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells? Cell Stem Cell  2015; 16(3): 225-38.
 [http://dx.doi.org/10.1016/j.stem.2015.02.015] [PMID:  25748930]

[114]
Anding AL, Baehrecke EH. Cleaning house: Selective autophagy of organelles. Dev Cell  2017; 41(1): 10-22.
 [http://dx.doi.org/10.1016/j.devcel.2017.02.016] [PMID:  28399394]

[115]
Feng H, Wang J, Chen W, et al. Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance. J Bone Oncol  2016; 5(2): 67-73.
 [http://dx.doi.org/10.1016/j.jbo.2016.03.001] [PMID:  27335774]

[116]
Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat Rev Clin Oncol  2017; 14(10): 611-29.
 [http://dx.doi.org/10.1038/nrclinonc.2017.44] [PMID:  28397828]

[117]
Rajapakse A, Suraweera A, Boucher D, et al. Redox regulation in the base excision repair pathway: Old and new players as cancer therapeutic targets. Curr Med Chem  2020; 27(12): 1901-21.
 [http://dx.doi.org/10.2174/0929867326666190430092732] [PMID:  31258058]

[118]
Mandal PK, Blanpain C, Rossi DJ. DNA damage response in adult stem cells: Pathways and consequences. Nat Rev Mol Cell Biol  2011; 12(3): 198-202.
 [http://dx.doi.org/10.1038/nrm3060] [PMID:  21304553]

[119]
Ahmed SU, Carruthers R, Gilmour L, Yildirim S, Watts C, Chalmers AJ. Selective inhibition of parallel DNA damage response pathways optimizes radiosensitization of glioblastoma stem-like cells. Cancer Res  2015; 75(20): 4416-28.
 [http://dx.doi.org/10.1158/0008-5472.CAN-14-3790] [PMID:  26282173]

[120]
Carruthers R, Ahmed SU, Strathdee K, et al. Abrogation of radioresistance in glioblastoma stem-like cells by inhibition of ATM kinase. Mol Oncol  2015; 9(1): 192-203.
 [http://dx.doi.org/10.1016/j.molonc.2014.08.003] [PMID:  25205037]

[121]
Yang ZX, Sun YH, He JG, Cao H, Jiang GQ. Increased activity of CHK enhances the radioresistance of MCF-7 breast cancer stem cells. Oncol Lett  2015; 10(6): 3443-9.
 [http://dx.doi.org/10.3892/ol.2015.3777] [PMID:  26788148]

[122]
Desai A, Webb B, Gerson SL. CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells. Radiother Oncol  2014; 110(3): 538-45.
 [http://dx.doi.org/10.1016/j.radonc.2013.10.040] [PMID:  24440048]

[123]
Lim YC, Roberts TL, Day BW, et al. A role for homologous recombination and abnormal cell-cycle progression in radioresistance of glioma-initiating cells. Mol Cancer Ther  2012; 11(9): 1863-72.
 [http://dx.doi.org/10.1158/1535-7163.MCT-11-1044] [PMID:  22772423]

[124]
Balbous A, Cortes U, Guilloteau K, et al. A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells. BMC Cancer  2016; 16(1): 604.
 [http://dx.doi.org/10.1186/s12885-016-2647-9] [PMID:  27495836]

[125]
Dembinski JL, Krauss S. Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma. Clin Exp Metastasis  2009; 26(7): 611-23.
 [http://dx.doi.org/10.1007/s10585-009-9260-0] [PMID:  19421880]

[126]
Wang H, Bierie B, Li AG, et al. BRCA1/FANCD2/BRG1-driven DNA repair stabilizes the differentiation state of human mammary epithelial cells. Mol Cell  2016; 63(2): 277-92.
 [http://dx.doi.org/10.1016/j.molcel.2016.05.038] [PMID:  27373334]

[127]
Ding S, Li C, Cheng N, Cui X, Xu X, Zhou G. Redox regulation in cancer stem cells. Oxid Med Cell Longev  2015; 2015: 750798.
 [http://dx.doi.org/10.1155/2015/750798]

[128]
DeNicola GM, Karreth FA, Humpton TJ, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature  2011; 475(7354): 106-9.
 [http://dx.doi.org/10.1038/nature10189] [PMID:  21734707]

[129]
Ryoo IG, Lee SH, Kwak MK. Redox modulating NRF2: A potential mediator of cancer stem cell resistance. Oxid Med Cell Longev  2016; 2016: 2428153.
 [http://dx.doi.org/10.1155/2016/2428153]

[130]
Jeong Y, Hoang NT, Lovejoy A, et al. Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiation resistance. Cancer Discov  2017; 7(1): 86-101.
 [http://dx.doi.org/10.1158/2159-8290.CD-16-0127] [PMID:  27663899]

[131]
Ritchie KE, Nör JE. Perivascular stem cell niche in head and neck cancer. Cancer Lett  2013; 338(1): 41-6.
 [http://dx.doi.org/10.1016/j.canlet.2012.07.025] [PMID:  22842095]

[132]
Oshimori N, Guo Y, Taniguchi S. An emerging role for cellular crosstalk in the cancer stem cell niche. J Pathol  2021; 254(4): 384-94.
 [http://dx.doi.org/10.1002/path.5655] [PMID:  33634866]

[133]
Jin MH, Oh DY. ATM in DNA repair in cancer. Pharmacol Ther  2019; 203: 107391.
 [http://dx.doi.org/10.1016/j.pharmthera.2019.07.002] [PMID:  31299316]

[134]
Venere M, Hamerlik P, Wu Q, et al. Therapeutic targeting of constitutive PARP activation compromises stem cell phenotype and survival of glioblastoma-initiating cells. Cell Death Differ  2014; 21(2): 258-69.
 [http://dx.doi.org/10.1038/cdd.2013.136] [PMID:  24121277]

[135]
Lesueur P, Chevalier F, El-Habr EA, et al. Radiosensitization effect of talazoparib, a parp inhibitor, on glioblastoma stem cells exposed to low and high linear energy transfer radiation. Sci Rep  2018; 8(1): 3664.
 [http://dx.doi.org/10.1038/s41598-018-22022-4] [PMID:  29483558]

[136]
Tangutoori S, Baldwin P, Sridhar S. PARP inhibitors: A new era of targeted therapy. Maturitas  2015; 81(1): 5-9.
 [http://dx.doi.org/10.1016/j.maturitas.2015.01.015] [PMID:  25708226]

[137]
Kelley MR, Logsdon D, Fishel ML. Targeting DNA repair pathways for cancer treatment: What’s new? Future Oncol  2014; 10(7): 1215-37.
 [http://dx.doi.org/10.2217/fon.14.60] [PMID:  24947262]

[138]
Colak S, Medema JP. Cancer stem cells - important players in tumor therapy resistance. FEBS J  2014; 281(21): 4779-91.
 [http://dx.doi.org/10.1111/febs.13023] [PMID:  25158828]

[139]
Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci  2018; 25(1): 20.
 [http://dx.doi.org/10.1186/s12929-018-0426-4] [PMID:  29506506]

[140]
Filipponi D, Emelyanov A, Muller J, Molina C, Nichols J, Bulavin DV. DNA damage signaling-induced cancer cell reprogramming as a driver of tumor relapse. Mol Cell  2019; 74(4): 651-63. e8.
 [http://dx.doi.org/10.1016/j.molcel.2019.03.002] [PMID: 30954402]

[141]
Zhang Z, Han H, Rong Y, et al. Hypoxia potentiates gemcitabine-induced stemness in pancreatic cancer cells through AKT/Notch1 signaling. J Exp Clin Cancer Res  2018; 37(1): 291.
 [http://dx.doi.org/10.1186/s13046-018-0972-3] [PMID:  30486896]

[142]
Li Z. CD133: A stem cell biomarker and beyond. Exp Hematol Oncol  2013; 2(1): 17.
 [http://dx.doi.org/10.1186/2162-3619-2-17] [PMID:  23815814]

[143]
Mishra K. Intracellular reactive oxygen species determine cancer stem cell radiosensitivity related to predictive biomarker for radiotherapy. J Radiat Res  2018; 9(4): 147.
 [http://dx.doi.org/10.4103/jrcr.jrcr_1_19]

[144]
Lin J, Xia L, Liang J, et al. The roles of glucose metabolic reprogramming in chemo- and radio-resistance. J Exp Clin Cancer Res  2019; 38(1): 218.
 [http://dx.doi.org/10.1186/s13046-019-1214-z] [PMID:  31122265]

[145]
Efroni S, Duttagupta R, Cheng J, et al. Global transcription in pluripotent embryonic stem cells. Cell Stem Cell  2008; 2(5): 437-47.
 [http://dx.doi.org/10.1016/j.stem.2008.03.021] [PMID:  18462694]

[146]
Villicaña C, Cruz G, Zurita M. The basal transcription machinery as a target for cancer therapy. Cancer Cell Int  2014; 14(1): 18.
 [http://dx.doi.org/10.1186/1475-2867-14-18] [PMID:  24576043]

[147]
Yan N, Xu L, Wu X, et al. GSKJ4, an H3K27me3 demethylase inhibitor, effectively suppresses the breast cancer stem cells. Exp Cell Res  2017; 359(2): 405-14.
 [http://dx.doi.org/10.1016/j.yexcr.2017.08.024] [PMID:  28823831]

[148]
Ying M, Tilghman J, Wei Y, et al. Kruppel-like factor-9 (KLF9) inhibits glioblastoma stemness through global transcription repression and integrin α6 inhibition. J Biol Chem  2014; 289(47): 32742-56.
 [http://dx.doi.org/10.1074/jbc.M114.588988] [PMID:  25288800]

[149]
Caslini C, Hong S, Ban YJ, Chen XS, Ince TA. HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells. Oncogene  2019; 38(39): 6599-614.
 [http://dx.doi.org/10.1038/s41388-019-0897-0] [PMID:  31375747]

[150]
Zhang J, Liu S, Ye Q, Pan J. Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma. Mol Cancer  2019; 18(1): 140.
 [http://dx.doi.org/10.1186/s12943-019-1070-7] [PMID:  31526394]

[151]
Weinberg SE, Chandel NS. Targeting mitochondria metabolism for cancer therapy. Nat Chem Biol  2015; 11(1): 9-15.
 [http://dx.doi.org/10.1038/nchembio.1712] [PMID:  25517383]

[152]
Boland ML, Chourasia AH, Macleod KF. Mitochondrial dysfunction in cancer. Front Oncol  2013; 3: 292.
 [http://dx.doi.org/10.3389/fonc.2013.00292] [PMID:  24350057]

[153]
Ghosh P, Vidal C, Dey S, Zhang L. Mitochondria targeting as an effective strategy for cancer therapy. Int J Mol Sci  2020; 21(9): 3363.
 [http://dx.doi.org/10.3390/ijms21093363] [PMID:  32397535]

[154]
García-Heredia JM, Carnero A. Role of mitochondria in cancer stem cell resistance. Cells  2020; 9(7): 1693.
 [http://dx.doi.org/10.3390/cells9071693] [PMID:  32679735]

[155]
Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci USA  2013; 110(3): 972-7.
 [http://dx.doi.org/10.1073/pnas.1221055110] [PMID:  23277563]

[156]
Alvero AB, Montagna MK, Holmberg JC, Craveiro V, Brown D, Mor G. Targeting the mitochondria activates two independent cell death pathways in ovarian cancer stem cells. Mol Cancer Ther  2011; 10(8): 1385-93.
 [http://dx.doi.org/10.1158/1535-7163.MCT-11-0023] [PMID:  21677151]

[157]
Candas D, Lu CL, Fan M, et al. Mitochondrial MKP1 is a target for therapy-resistant HER2-positive breast cancer cells. Cancer Res  2014; 74(24): 7498-509.
 [http://dx.doi.org/10.1158/0008-5472.CAN-14-0844] [PMID:  25377473]

[158]
Song IS, Jeong JY, Jeong SH, et al. Mitochondria as therapeutic targets for cancer stem cells. World J Stem Cells  2015; 7(2): 418-27.
 [http://dx.doi.org/10.4252/wjsc.v7.i2.418] [PMID:  25815125]

[159]
Ali Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ. Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci  2020; 21(5): 1723.
 [http://dx.doi.org/10.3390/ijms21051723] [PMID:  32138313]

[160]
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell  2009; 136(4): 629-41.
 [http://dx.doi.org/10.1016/j.cell.2009.02.006] [PMID:  19239885]

[161]
Cao J. The functional role of long non-coding RNAs and epigenetics. Biol Proced Online  2014; 16(1): 42.
 [http://dx.doi.org/10.1186/1480-9222-16-11] [PMID:  24406024]

[162]
Takahashi R, Miyazaki H, Ochiya T. The role of microRNAs in the regulation of cancer stem cells. Front Genet  2014; 4: 295.
 [http://dx.doi.org/10.3389/fgene.2013.00295] [PMID:  24427168]

[163]
Zhuang J, Shen L, Yang L, et al. TGFβ1 promotes gemicitabine resistance through regulating the LncRNA-LET/NF90/mir-145 signalling axis in bladder cancer. Theranostics  2017; 7(12): 3053-67.
 [http://dx.doi.org/10.7150/thno.19542] [PMID:  28839463]

[164]
Wang L, Dong P, Wang W, Huang M, Tian B. Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem like cells via induction of lncRNA HOTAIR. Exp Ther Med  2017; 14(5): 4773-80.
 [http://dx.doi.org/10.3892/etm.2017.5151] [PMID:  29201179]

[165]
Hu Q, Ye Y, Chan LC, et al. Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nat Immunol  2019; 20(7): 835-51.
 [http://dx.doi.org/10.1038/s41590-019-0400-7] [PMID:  31160797]

[166]
Asadzadeh Z, Mansoori B, Mohammadi A, et al. microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities. J Cell Physiol  2019; 234(7): 10002-17.
 [http://dx.doi.org/10.1002/jcp.27885] [PMID:  30537109]

[167]
Karimi Dermani F, Amini R, Saidijam M, Najafi R. Retracted: miR‐200c, a tumor suppressor that modulate the expression of cancer stem cells markers and epithelial‐mesenchymal transition in colorectal cancer. J Cell Biochem  2018; 119(7): 6288-95.
 [http://dx.doi.org/10.1002/jcb.26880] [PMID:  29663476]

[168]
Li WJ, Wang Y, Liu R, et al. MicroRNA-34a: Potent tumor sup- pressor, cancer stem cell inhibitor, and potential anticancer thera- peutic. Front Cell Dev Biol  2021; 9: 640587.
 [http://dx.doi.org/10.3389/fcell.2021.640587] [PMID:  33763422]

[169]
Wang X, Meng Q, Qiao W, et al. miR-181b/Notch2 overcome chemoresistance by regulating cancer stem cell-like properties in NSCLC. Stem Cell Res Ther  2018; 9(1): 327.
 [http://dx.doi.org/10.1186/s13287-018-1072-1] [PMID:  30470250]

[170]
Jeong JY, Kang H, Kim TH, et al. MicroRNA-136 inhibits cancer stem cell activity and enhances the anti-tumor effect of paclitaxel against chemoresistant ovarian cancer cells by targeting Notch3. Cancer Lett  2017; 386: 168-78.
 [http://dx.doi.org/10.1016/j.canlet.2016.11.017] [PMID:  27887917]

[171]
Cheng M, Duan PG, Gao ZZ, Dai M. MicroRNA 487b 3p inhibits osteosarcoma chemoresistance and metastasis by targeting ALDH1A3. Oncol Rep  2020; 44(6): 2691-700.
 [http://dx.doi.org/10.3892/or.2020.7814] [PMID:  33125503]

[172]
Troschel FM, Böhly N, Borrmann K, et al. miR-142-3p attenuates breast cancer stem cell characteristics and decreases radioresistance in vitro. Tumour Biol  2018; 40(8): 1010428318791887.
 [http://dx.doi.org/10.1177/1010428318791887] [PMID:  30091683]

[173]
Masadah R, Rauf S, Pratama MY, Tiribelli C, Pascut D. The role of microRNAs in the cisplatin- and radio-resistance of cervical can- cer. Cancers  2021; 13(5): 1168.
 [http://dx.doi.org/10.3390/cancers13051168] [PMID:  33803151]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1574888X17666221003125208	Print ISSN 1574-888X
Publisher Name Bentham Science Publisher	Online ISSN 2212-3946
Current Stem Cell Research & Therapy

Stem Cells: Therapeutic Implications in Chemotherapy and Radiotherapy Resistance in Cancer Therapy

Abstract Play Pause

Graphical Abstract

Related Books

Abstract
