Abstract
Cancer stem cells (CSCs) are correlated with poor clinical outcomes due to their contribution to chemotherapy resistance and the formation of metastasis. Multiple cell surface and enzymatic markers have been characterized to identify CSCs, which is important for diagnosis, therapy, and prognosis. This review underlines the role of CSCs and circulating tumor cells (CTCs) in tumor relapse and metastasis, the characteristics of CSC and CTC biomarkers, and the techniques used to detect these cells.
We also summarized novel therapeutic approaches toward targeting CSCs, especially focusing on the role of immune checkpoint blockades (ICB), such as anti-programmed death 1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PDL1) therapies. Additionally, we address an intriguing new mechanism of action for small molecular drugs, such as telomere-targeted therapy 6-thio-2’deoxyguanosine (6- thio-dG), and how it reshapes tumor microenvironment to overcome ICB resistance. There are indications, that personalized cancer therapy targeting CSC populations in conjunction with immune-mediated strategy hold promise for the removal of residual therapy-resistant CSCs in the near future.
Graphical Abstract
[1]
Patel P, Chen EI. Cancer stem cells, tumor dormancy, and metastasis. Front Endocrinol 2012; 3: 125.
[http://dx.doi.org/10.3389/fendo.2012.00125] [PMID: 23109929]
[http://dx.doi.org/10.3389/fendo.2012.00125] [PMID: 23109929]
[2]
Sotiropoulou PA, Christodoulou MS, Silvani A, Herold MC, Passarella D. Chemical approaches to targeting drug resistance in cancer stem cells. Drug Discov Today 2014; 19(10): 1547-62.
[http://dx.doi.org/10.1016/j.drudis.2014.05.002] [PMID: 24819719]
[http://dx.doi.org/10.1016/j.drudis.2014.05.002] [PMID: 24819719]
[3]
Maccalli C, Rasul KI, Elawad M, Ferrone S. The role of cancer stem cells in the modulation of anti-tumor immune responses. Semin Cancer Biol 2018; 53: 189-200.
[http://dx.doi.org/10.1016/j.semcancer.2018.09.006] [PMID: 30261276]
[http://dx.doi.org/10.1016/j.semcancer.2018.09.006] [PMID: 30261276]
[4]
Chang JC. Cancer stem cells. Medicine 2016; 95(1S): S20-5.
[http://dx.doi.org/10.1097/MD.0000000000004766] [PMID: 27611935]
[http://dx.doi.org/10.1097/MD.0000000000004766] [PMID: 27611935]
[5]
Yoshida GJ, Saya H. Therapeutic strategies targeting cancer stem cells. Cancer Sci 2016; 107(1): 5-11.
[http://dx.doi.org/10.1111/cas.12817] [PMID: 26362755]
[http://dx.doi.org/10.1111/cas.12817] [PMID: 26362755]
[6]
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]
[http://dx.doi.org/10.1016/j.pharmthera.2016.02.008] [PMID: 26899500]
[7]
Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell 2014; 14(3): 275-91.
[http://dx.doi.org/10.1016/j.stem.2014.02.006] [PMID: 24607403]
[http://dx.doi.org/10.1016/j.stem.2014.02.006] [PMID: 24607403]
[8]
Annett S, Robson T. Targeting cancer stem cells in the clinic: Current status and perspectives. Pharmacol Ther 2018; 187: 13-30.
[http://dx.doi.org/10.1016/j.pharmthera.2018.02.001] [PMID: 29421575]
[http://dx.doi.org/10.1016/j.pharmthera.2018.02.001] [PMID: 29421575]
[9]
Vadakke MS, Limaye LS, Kale VP, Chaudhry HW. Flow cytometry and cell sorting using hematopoietic progenitor cells. Methods Mol Biol 2019; 2029: 235-46.
[http://dx.doi.org/10.1007/978-1-4939-9631-5_18] [PMID: 31273746]
[http://dx.doi.org/10.1007/978-1-4939-9631-5_18] [PMID: 31273746]
[10]
Chen T, Li J, Jia Y, et al. Single-cell sequencing in the field of stem cells. Curr Genomics 2020; 21(8): 576-84.
[http://dx.doi.org/10.2174/1389202921999200624154445] [PMID: 33414679]
[http://dx.doi.org/10.2174/1389202921999200624154445] [PMID: 33414679]
[11]
Yu Z, Pestell TG, Lisanti MP, Pestell RG. Cancer stem cells. Int J Biochem Cell Biol 2012; 44(12): 2144-51.
[http://dx.doi.org/10.1016/j.biocel.2012.08.022] [PMID: 22981632]
[http://dx.doi.org/10.1016/j.biocel.2012.08.022] [PMID: 22981632]
[12]
Toledo GME, Hernández MI, Gómez GÁA, Ortiz SE. ALDH as a stem cell marker in solid tumors. Curr Stem Cell Res Ther 2019; 14(5): 375-88.
[http://dx.doi.org/10.2174/1574888X13666180810120012] [PMID: 30095061]
[http://dx.doi.org/10.2174/1574888X13666180810120012] [PMID: 30095061]
[13]
Vassalli G. Aldehyde dehydrogenases: Not just markers, but functional regulators of stem cells. Stem Cells Int 2019; 2019: 3904645.
[http://dx.doi.org/10.1155/2019/3904645] [PMID: 30733805]
[http://dx.doi.org/10.1155/2019/3904645] [PMID: 30733805]
[14]
Katsuno Y, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, Miyazono K. Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-β. J Pathol 2012; 228(3): 391-404.
[http://dx.doi.org/10.1002/path.4020] [PMID: 22430847]
[http://dx.doi.org/10.1002/path.4020] [PMID: 22430847]
[15]
Cho Y, Kim YK. Cancer stem cells as a potential target to overcome multidrug resistance. Front Oncol 2020; 10: 764.
[http://dx.doi.org/10.3389/fonc.2020.00764] [PMID: 32582535]
[http://dx.doi.org/10.3389/fonc.2020.00764] [PMID: 32582535]
[16]
Han SH, Kim J, Kim M, et al. Prognostic implication of ABC transporters and cancer stem cell markers in patients with stage III colon cancer receiving adjuvant FOLFOX 4 chemotherapy. Oncol Lett 2019; 17(6): 5572-80.
[http://dx.doi.org/10.3892/ol.2019.10234] [PMID: 31186779]
[http://dx.doi.org/10.3892/ol.2019.10234] [PMID: 31186779]
[17]
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]
[http://dx.doi.org/10.3390/ijms18112362] [PMID: 29117122]
[18]
Ortiz MP, Liu BWY, Londoño VA, Vernot JP. CD24 expression and stem-associated features define tumor cell heterogeneity and tumorigenic capacities in a model of carcinogenesis. Cancer Manag Res 2018; 10: 5767-84.
[http://dx.doi.org/10.2147/CMAR.S176654] [PMID: 30510447]
[http://dx.doi.org/10.2147/CMAR.S176654] [PMID: 30510447]
[19]
Calaf G, Ponce CR, Abarca QJ. Effect of curcumin on the cell surface markers CD44 and CD24 in breast cancer. Oncol Rep 2018; 39(6): 2741-8.
[http://dx.doi.org/10.3892/or.2018.6386] [PMID: 29693159]
[http://dx.doi.org/10.3892/or.2018.6386] [PMID: 29693159]
[20]
Thapa R, Wilson GD. The importance of CD44 as a stem cell biomarker and therapeutic target in cancer. Stem Cells Int 2016; 2016: 2087204.
[http://dx.doi.org/10.1155/2016/2087204] [PMID: 27200096]
[http://dx.doi.org/10.1155/2016/2087204] [PMID: 27200096]
[21]
Xu H, Niu M, Yuan X, Wu K, Liu A. CD44 as a tumor biomarker and therapeutic target. Exp Hematol Oncol 2020; 9(1): 36.
[http://dx.doi.org/10.1186/s40164-020-00192-0] [PMID: 33303029]
[http://dx.doi.org/10.1186/s40164-020-00192-0] [PMID: 33303029]
[22]
Jaggupilli A, Elkord E. Significance of CD44 and CD24 as cancer stem cell markers: An enduring ambiguity. Clin Dev Immunol 2012; 2012: 708036.
[http://dx.doi.org/10.1155/2012/708036] [PMID: 22693526]
[http://dx.doi.org/10.1155/2012/708036] [PMID: 22693526]
[23]
Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions. Nat Rev Cancer 2008; 8(10): 755-68.
[http://dx.doi.org/10.1038/nrc2499] [PMID: 18784658]
[http://dx.doi.org/10.1038/nrc2499] [PMID: 18784658]
[24]
Beça FF, Caetano P, Gerhard R, et al. Cancer stem cells markers CD44, CD24 and ALDH1 in breast cancer special histological types. J Clin Pathol 2013; 66(3): 187-91.
[http://dx.doi.org/10.1136/jclinpath-2012-201169] [PMID: 23112116]
[http://dx.doi.org/10.1136/jclinpath-2012-201169] [PMID: 23112116]
[25]
Sauzay C, Voutetakis K, Chatziioannou A, Chevet E, Avril T. CD90/Thy-1, a cancer-associated cell surface signaling molecule. Front Cell Dev Biol 2019; 7: 66.
[http://dx.doi.org/10.3389/fcell.2019.00066] [PMID: 31080802]
[http://dx.doi.org/10.3389/fcell.2019.00066] [PMID: 31080802]
[26]
Jiang J, Zhang Y, Chuai S, et al. Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype. Oncogene 2012; 31(6): 671-82.
[http://dx.doi.org/10.1038/onc.2011.282] [PMID: 21743497]
[http://dx.doi.org/10.1038/onc.2011.282] [PMID: 21743497]
[27]
Barzegar BA, Syahir A, Ahmad S. CD133: Beyond a cancer stem cell biomarker. J Drug Target 2019; 27(3): 257-69.
[http://dx.doi.org/10.1080/1061186X.2018.1479756] [PMID: 29911902]
[http://dx.doi.org/10.1080/1061186X.2018.1479756] [PMID: 29911902]
[28]
Liou GY. CD133 as a regulator of cancer metastasis through the cancer stem cells. Int J Biochem Cell Biol 2019; 106: 1-7.
[http://dx.doi.org/10.1016/j.biocel.2018.10.013] [PMID: 30399449]
[http://dx.doi.org/10.1016/j.biocel.2018.10.013] [PMID: 30399449]
[29]
Tsunekuni K, Konno M, Haraguchi N, et al. CD44/CD133-positive colorectal cancer stem cells are sensitive to trifluridine exposure. Sci Rep 2019; 9(1): 14861.
[http://dx.doi.org/10.1038/s41598-019-50968-6] [PMID: 31619711]
[http://dx.doi.org/10.1038/s41598-019-50968-6] [PMID: 31619711]
[30]
Park DJ, Sung PS, Kim JH, et al. EpCAM-high liver cancer stem cells resist natural killer cell–mediated cytotoxicity by upregulating CEACAM1. J Immunother Cancer 2020; 8(1): e000301.
[http://dx.doi.org/10.1136/jitc-2019-000301] [PMID: 32221015]
[http://dx.doi.org/10.1136/jitc-2019-000301] [PMID: 32221015]
[31]
Vasanthakumar S, Sasikala P, Padma M, Balachandar V, Venkatesh B, Ganesan S. EpCAM as a novel therapeutic target for hepatocellular carcinoma. J Oncol 2017; 3(2): 71-6.
[http://dx.doi.org/10.1016/j.jons.2017.04.002]
[http://dx.doi.org/10.1016/j.jons.2017.04.002]
[32]
Firtina KZ, Akbari S, Karabicici M, et al. A novel function for KLF4 in modulating the de-differentiation of EpCAM−/CD133−nonStem Cells into EpCAM+/CD133+ liver cancer stem cells in HCC cell line HuH7. Cells 2020; 9(5): 1198.
[http://dx.doi.org/10.3390/cells9051198] [PMID: 32408542]
[http://dx.doi.org/10.3390/cells9051198] [PMID: 32408542]
[33]
Salcido CD, Larochelle A, Taylor BJ, Dunbar CE, Varticovski L. Molecular characterisation of side population cells with cancer stem cell-like characteristics in small-cell lung cancer. Br J Cancer 2010; 102(11): 1636-44.
[http://dx.doi.org/10.1038/sj.bjc.6605668] [PMID: 20424609]
[http://dx.doi.org/10.1038/sj.bjc.6605668] [PMID: 20424609]
[34]
Liu Y, Cui P, Chen J, Li W. Isolation and phenotypic characterization of side population cells in oral squamous cell carcinoma. Mol Med Rep 2015; 11(5): 3642-6.
[http://dx.doi.org/10.3892/mmr.2014.3133] [PMID: 25544110]
[http://dx.doi.org/10.3892/mmr.2014.3133] [PMID: 25544110]
[35]
Aboulkheyr Es H, Bigdeli B, Zhand S, Aref AR, Thiery JP, Warkiani ME. Mesenchymal stem cells induce PD-L1 expression through the secretion of CCL5 in breast cancer cells. J Cell Physiol 2021; 236(5): 3918-28.
[http://dx.doi.org/10.1002/jcp.30135] [PMID: 33145762]
[http://dx.doi.org/10.1002/jcp.30135] [PMID: 33145762]
[36]
Darvin P, Sasidharan NV, Elkord E. PD-L1 expression in human breast cancer stem cells is epigenetically regulated through posttranslational histone modifications. J Oncol 2019; 2019: 3958908.
[http://dx.doi.org/10.1155/2019/3958908] [PMID: 30915120]
[http://dx.doi.org/10.1155/2019/3958908] [PMID: 30915120]
[37]
Dong P, Xiong Y, Yue J, Hanley SJB, Watari H. Tumor-intrinsic PD-L1 signaling in cancer initiation, development and treatment: Beyond immune evasion. Front Oncol 2018; 8: 386.
[http://dx.doi.org/10.3389/fonc.2018.00386] [PMID: 30283733]
[http://dx.doi.org/10.3389/fonc.2018.00386] [PMID: 30283733]
[38]
Zhang S, Xiong X, Sun Y. Functional characterization of SOX2 as an anticancer target. Signal Transduct Target Ther 2020; 5(1): 135.
[http://dx.doi.org/10.1038/s41392-020-00242-3] [PMID: 32728033]
[http://dx.doi.org/10.1038/s41392-020-00242-3] [PMID: 32728033]
[39]
Lundberg IV, Edin S, Eklöf V, Öberg Å, Palmqvist R, Wikberg ML. SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2 in colorectal cancer. BMC Cancer 2016; 16(1): 471.
[http://dx.doi.org/10.1186/s12885-016-2509-5] [PMID: 27411517]
[http://dx.doi.org/10.1186/s12885-016-2509-5] [PMID: 27411517]
[40]
Takeda K, Mizushima T, Yokoyama Y, et al. Sox2 is associated with cancer stem-like properties in colorectal cancer. Sci Rep 2018; 8(1): 17639.
[http://dx.doi.org/10.1038/s41598-018-36251-0] [PMID: 30518951]
[http://dx.doi.org/10.1038/s41598-018-36251-0] [PMID: 30518951]
[41]
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]
[http://dx.doi.org/10.3389/fimmu.2020.01280] [PMID: 32849491]
[42]
Liu Z, Zhang J, Kang H, et al. Significance of stem cell marker Nanog gene in the diagnosis and prognosis of lung cancer. Oncol Lett 2016; 12(4): 2507-10.
[http://dx.doi.org/10.3892/ol.2016.4923] [PMID: 27698819]
[http://dx.doi.org/10.3892/ol.2016.4923] [PMID: 27698819]
[43]
Mohan A, Raj RR, Mohan G. K PP, Maliekal TT. Reporters of cancer stem cells as a tool for drug discovery. Front Oncol 2021; 11: 669250.
[http://dx.doi.org/10.3389/fonc.2021.669250] [PMID: 33968778]
[http://dx.doi.org/10.3389/fonc.2021.669250] [PMID: 33968778]
[44]
Baek KH, Choi J, Pei CZ. Cellular functions of OCT-3/4 regulated by ubiquitination in proliferating cells. Cancers 2020; 12(3): 663.
[http://dx.doi.org/10.3390/cancers12030663] [PMID: 32178477]
[http://dx.doi.org/10.3390/cancers12030663] [PMID: 32178477]
[45]
Mohiuddin IS, Wei SJ, Kang MH. Role of OCT4 in cancer stem-like cells and chemotherapy resistance. Biochim Biophys Acta Mol Basis Dis 2020; 1866(4): 165432.
[http://dx.doi.org/10.1016/j.bbadis.2019.03.005] [PMID: 30904611]
[http://dx.doi.org/10.1016/j.bbadis.2019.03.005] [PMID: 30904611]
[46]
Rasti A, Mehrazma M, Madjd Z, Abolhasani M, Saeednejad ZL, Asgari M. Co-expression of cancer stem cell markers OCT4 and NANOG predicts poor prognosis in renal cell carcinomas. Sci Rep 2018; 8(1): 11739.
[http://dx.doi.org/10.1038/s41598-018-30168-4] [PMID: 30082842]
[http://dx.doi.org/10.1038/s41598-018-30168-4] [PMID: 30082842]
[47]
Meisel CT, Porcheri C, Mitsiadis TA. Cancer stem cells, Quo Vadis? The notch signaling pathway in tumor initiation and progression. Cells 2020; 9(8): 1879.
[http://dx.doi.org/10.3390/cells9081879] [PMID: 32796631]
[http://dx.doi.org/10.3390/cells9081879] [PMID: 32796631]
[48]
Edwards A, Brennan K. Notch signalling in breast development and cancer. Front Cell Dev Biol 2021; 9: 692173.
[http://dx.doi.org/10.3389/fcell.2021.692173] [PMID: 34295896]
[http://dx.doi.org/10.3389/fcell.2021.692173] [PMID: 34295896]
[49]
Below M, Osipo C. Notch signaling in breast cancer: A role in drug resistance. Cells 2020; 9(10): 2204.
[50]
Bigoni OGD, Czarnowski D, Parsons T, Madlambayan GJ, Villa DLG. Integrin α6 (CD49f), the microenvironment and cancer stem cells. Curr Stem Cell Res Ther 2019; 14(5): 428-36.
[http://dx.doi.org/10.2174/1574888X13666181002151330] [PMID: 30280675]
[http://dx.doi.org/10.2174/1574888X13666181002151330] [PMID: 30280675]
[51]
Haraguchi N, Ishii H, Mimori K, et al. CD49f-positive cell population efficiently enriches colon cancer-initiating cells. Int J Oncol 2013; 43(2): 425-30.
[http://dx.doi.org/10.3892/ijo.2013.1955] [PMID: 23708747]
[http://dx.doi.org/10.3892/ijo.2013.1955] [PMID: 23708747]
[52]
Krebsbach PH, Villa DLG. The role of integrin α6 (CD49f) in stem cells: More than a conserved biomarker. Stem Cells Dev 2017; 26(15): 1090-9.
[http://dx.doi.org/10.1089/scd.2016.0319] [PMID: 28494695]
[http://dx.doi.org/10.1089/scd.2016.0319] [PMID: 28494695]
[53]
Kalantari E, Taheri T, Fata S, et al. Significant co-expression of putative cancer stem cell markers, EpCAM and CD166, correlates with tumor stage and invasive behavior in colorectal cancer. World J Surg Oncol 2022; 20(1): 15.
[http://dx.doi.org/10.1186/s12957-021-02469-y] [PMID: 35016698]
[http://dx.doi.org/10.1186/s12957-021-02469-y] [PMID: 35016698]
[54]
Kim DK, Ham MH, Lee SY, et al. CD166 promotes the cancer stem-like properties of primary epithelial ovarian cancer cells. BMB Rep 2020; 53(12): 622-7.
[http://dx.doi.org/10.5483/BMBRep.2020.53.12.102] [PMID: 32843129]
[http://dx.doi.org/10.5483/BMBRep.2020.53.12.102] [PMID: 32843129]
[55]
Mahmoodi CG. CD166 as a stem cell marker? A potential target for therapy colorectal cancer? J Stem Cell Res Ther 2016; 1.
[56]
Zhang T, Kawaguchi N, Hayama E, Furutani Y, Nakanishi T. High expression of CXCR4 and stem cell markers in a monocrotaline and chronic hypoxia induced rat model of pulmonary arterial hypertension. Exp Ther Med 2018; 15(6): 4615-22.
[http://dx.doi.org/10.3892/etm.2018.6027] [PMID: 29805477]
[http://dx.doi.org/10.3892/etm.2018.6027] [PMID: 29805477]
[57]
Eckert F, Schilbach K, Klumpp L, et al. Potential role of CXCR4 targeting in the context of radiotherapy and immunotherapy of cancer. Front Immunol 2018; 9: 3018.
[http://dx.doi.org/10.3389/fimmu.2018.03018] [PMID: 30622535]
[http://dx.doi.org/10.3389/fimmu.2018.03018] [PMID: 30622535]
[58]
Trautmann F, Cojoc M, Kurth I, et al. CXCR4 as biomarker for radioresistant cancer stem cells. Int J Radiat Biol 2014; 90(8): 687-99.
[http://dx.doi.org/10.3109/09553002.2014.906766] [PMID: 24650104]
[http://dx.doi.org/10.3109/09553002.2014.906766] [PMID: 24650104]
[59]
López GJC, Martin HL, Hermann PC, Sainz B Jr. The CXCL12 crossroads in cancer stem cells and their niche. Cancers 2021; 13(3): 469.
[http://dx.doi.org/10.3390/cancers13030469] [PMID: 33530455]
[http://dx.doi.org/10.3390/cancers13030469] [PMID: 33530455]
[60]
Bianchi ME, Mezzapelle R. The chemokine receptor CXCR4 in cell proliferation and tissue regeneration. Front Immunol 2020; 11: 2109.
[http://dx.doi.org/10.3389/fimmu.2020.02109] [PMID: 32983169]
[http://dx.doi.org/10.3389/fimmu.2020.02109] [PMID: 32983169]
[61]
Fujita T, Chiwaki F, Takahashi R, et al. Identification and characterization of CXCR4-positive gastric cancer stem cells. PLoS One 2015; 10(6): e0130808.
[http://dx.doi.org/10.1371/journal.pone.0130808] [PMID: 26110809]
[http://dx.doi.org/10.1371/journal.pone.0130808] [PMID: 26110809]
[62]
Cao HZ, Liu XF, Yang WT, Chen Q, Zheng PS. LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer. Cell Death Dis 2017; 8(9): e3039.
[http://dx.doi.org/10.1038/cddis.2017.393] [PMID: 28880275]
[http://dx.doi.org/10.1038/cddis.2017.393] [PMID: 28880275]
[63]
Xu L, Lin W, Wen L, Li G. Lgr5 in cancer biology: Functional identification of Lgr5 in cancer progression and potential opportunities for novel therapy. Stem Cell Res Ther 2019; 10(1): 219.
[http://dx.doi.org/10.1186/s13287-019-1288-8] [PMID: 31358061]
[http://dx.doi.org/10.1186/s13287-019-1288-8] [PMID: 31358061]
[64]
Morgan RG, Mortensson E, Williams AC. Targeting LGR5 in colorectal cancer: Therapeutic gold or too plastic? Br J Cancer 2018; 118(11): 1410-8.
[http://dx.doi.org/10.1038/s41416-018-0118-6] [PMID: 29844449]
[http://dx.doi.org/10.1038/s41416-018-0118-6] [PMID: 29844449]
[65]
Leng Z, Xia Q, Chen J, et al. Lgr5+CD44+EpCAM+ strictly defines cancer stem cells in human colorectal cancer. Cell Physiol Biochem 2018; 46(2): 860-72.
[http://dx.doi.org/10.1159/000488743] [PMID: 29627827]
[http://dx.doi.org/10.1159/000488743] [PMID: 29627827]
[66]
Pastrana E, Silvan VV, Doetsch F. Eyes wide open: A critical review of sphere-formation as an assay for stem cells. Cell Stem Cell 2011; 8(5): 486-98.
[http://dx.doi.org/10.1016/j.stem.2011.04.007] [PMID: 21549325]
[http://dx.doi.org/10.1016/j.stem.2011.04.007] [PMID: 21549325]
[67]
Harper LJ, Piper K, Common J, Fortune F, Mackenzie IC. Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J Oral Pathol Med 2007; 36(10): 594-603.
[http://dx.doi.org/10.1111/j.1600-0714.2007.00617.x] [PMID: 17944752]
[http://dx.doi.org/10.1111/j.1600-0714.2007.00617.x] [PMID: 17944752]
[68]
Li H, Chen X, Calhoun DT, Claypool K, Tang DG. PC3 human prostate carcinoma cell holoclones contain self-renewing tumor-initiating cells. Cancer Res 2008; 68(6): 1820-5.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5878] [PMID: 18339862]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5878] [PMID: 18339862]
[69]
Guddati AK. Ovarian cancer stem cells: Elusive targets for chemotherapy. Med Oncol 2012; 29(5): 3400-8.
[http://dx.doi.org/10.1007/s12032-012-0252-6] [PMID: 22638913]
[http://dx.doi.org/10.1007/s12032-012-0252-6] [PMID: 22638913]
[70]
McClellan S, Slamecka J, Howze P, et al. mRNA detection in living cells: A next generation cancer stem cell identification technique. Methods 2015; 82: 47-54.
[http://dx.doi.org/10.1016/j.ymeth.2015.04.022] [PMID: 25920950]
[http://dx.doi.org/10.1016/j.ymeth.2015.04.022] [PMID: 25920950]
[71]
Blackburn JS, Liu S, Langenau DM. Quantifying the frequency of tumor-propagating cells using limiting dilution cell transplantation in syngeneic zebrafish. J Vis Exp 2011; (53): e2790.
[http://dx.doi.org/10.3791/2790] [PMID: 21775966]
[http://dx.doi.org/10.3791/2790] [PMID: 21775966]
[72]
Illa BI, Fernandez GR, Shelton DN, Welm BE, De Solorzano OC, Barcellos HMH. Limiting-dilution transplantation assays in mammary stem cell studies. Methods Mol Biol 2010; 621: 29-47.
[http://dx.doi.org/10.1007/978-1-60761-063-2_2] [PMID: 20405357]
[http://dx.doi.org/10.1007/978-1-60761-063-2_2] [PMID: 20405357]
[73]
Guil LS, Sedlik C, Piaggio E. Humanized mouse models to evaluate cancer immunotherapeutics. Annu Rev Cancer Biol 2021; 5(1): 119-36.
[http://dx.doi.org/10.1146/annurev-cancerbio-050520-100526]
[http://dx.doi.org/10.1146/annurev-cancerbio-050520-100526]
[74]
Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell 2017; 168(4): 670-91.
[http://dx.doi.org/10.1016/j.cell.2016.11.037] [PMID: 28187288]
[http://dx.doi.org/10.1016/j.cell.2016.11.037] [PMID: 28187288]
[75]
Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nat Rev Cancer 2004; 4(6): 448-56.
[http://dx.doi.org/10.1038/nrc1370] [PMID: 15170447]
[http://dx.doi.org/10.1038/nrc1370] [PMID: 15170447]
[76]
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]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[77]
Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 2008; 8(5): 329-40.
[http://dx.doi.org/10.1038/nrc2375] [PMID: 18404148]
[http://dx.doi.org/10.1038/nrc2375] [PMID: 18404148]
[78]
Ashworth T. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Australas Med J 1869; 14: 146-7.
[79]
Chemi F, Mohan S, Guevara T, Clipson A, Rothwell DG, Dive C. Early dissemination of circulating tumor cells: Biological and clinical insights. Front Oncol 2021; 11: 672195.
[http://dx.doi.org/10.3389/fonc.2021.672195] [PMID: 34026650]
[http://dx.doi.org/10.3389/fonc.2021.672195] [PMID: 34026650]
[80]
Schuettpelz LG, Link DC. Niche competition and cancer metastasis to bone. J Clin Invest 2011; 121(4): 1253-5.
[http://dx.doi.org/10.1172/JCI57229] [PMID: 21436576]
[http://dx.doi.org/10.1172/JCI57229] [PMID: 21436576]
[81]
Shiozawa Y, Pedersen EA, Havens AM, et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest 2011; 121(4): 1298-312.
[http://dx.doi.org/10.1172/JCI43414] [PMID: 21436587]
[http://dx.doi.org/10.1172/JCI43414] [PMID: 21436587]
[82]
Aguirre GJA. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 2007; 7(11): 834-46.
[http://dx.doi.org/10.1038/nrc2256] [PMID: 17957189]
[http://dx.doi.org/10.1038/nrc2256] [PMID: 17957189]
[83]
Pantel K, Alix PC, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol 2009; 6(6): 339-51.
[http://dx.doi.org/10.1038/nrclinonc.2009.44] [PMID: 19399023]
[http://dx.doi.org/10.1038/nrclinonc.2009.44] [PMID: 19399023]
[84]
Aguirre GJA. On the theory of tumor self-seeding: Implications for metastasis progression in humans. Breast Cancer Res 2010; 12(2): 304.
[http://dx.doi.org/10.1186/bcr2561] [PMID: 20459594]
[http://dx.doi.org/10.1186/bcr2561] [PMID: 20459594]
[85]
Kim MY, Oskarsson T, Acharyya S, et al. Tumor self-seeding by circulating cancer cells. Cell 2009; 139(7): 1315-26.
[http://dx.doi.org/10.1016/j.cell.2009.11.025] [PMID: 20064377]
[http://dx.doi.org/10.1016/j.cell.2009.11.025] [PMID: 20064377]
[86]
Alix PC, Schwarzenbach H, Pantel K. Circulating tumor cells and circulating tumor DNA. Annu Rev Med 2012; 63(1): 199-215.
[http://dx.doi.org/10.1146/annurev-med-062310-094219] [PMID: 22053740]
[http://dx.doi.org/10.1146/annurev-med-062310-094219] [PMID: 22053740]
[87]
Zhou J, Zhu X, Wu S, et al. Epithelial-mesenchymal transition status of circulating tumor cells in breast cancer and its clinical relevance. Cancer Biol Med 2020; 17(1): 169-80.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0118] [PMID: 32296584]
[http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0118] [PMID: 32296584]
[88]
Greystoke A, Dean E, Saunders MP, et al. Multi-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancer. Br J Cancer 2012; 107(9): 1518-24.
[http://dx.doi.org/10.1038/bjc.2012.416] [PMID: 22996610]
[http://dx.doi.org/10.1038/bjc.2012.416] [PMID: 22996610]
[89]
Nicolazzo C, Raimondi C, Francescangeli F, et al. EpCAM-expressing circulating tumor cells in colorectal cancer. Int J Biol Markers 2017; 32(4): 415-20.
[http://dx.doi.org/10.5301/ijbm.5000284] [PMID: 28604994]
[http://dx.doi.org/10.5301/ijbm.5000284] [PMID: 28604994]
[90]
Ning Y, Zhang W, Hanna DL, et al. Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients. Pharmacogenomics J 2018; 18(1): 29-34.
[http://dx.doi.org/10.1038/tpj.2016.62] [PMID: 27503579]
[http://dx.doi.org/10.1038/tpj.2016.62] [PMID: 27503579]
[91]
Zhao R, Cai Z, Li S, et al. Expression and clinical relevance of epithelial and mesenchymal markers in circulating tumor cells from colorectal cancer. Oncotarget 2017; 8(6): 9293-302.
[http://dx.doi.org/10.18632/oncotarget.14065] [PMID: 28030836]
[http://dx.doi.org/10.18632/oncotarget.14065] [PMID: 28030836]
[92]
Lindsay CR, Faugeroux V, Michiels S, et al. A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups. Ann Oncol 2017; 28(7): 1523-31.
[http://dx.doi.org/10.1093/annonc/mdx156] [PMID: 28633480]
[http://dx.doi.org/10.1093/annonc/mdx156] [PMID: 28633480]
[93]
Tamminga M, De Wit S, Van De Wauwer C, et al. Analysis of released circulating tumor cells during surgery for non-small cell lung cancer. Clin Cancer Res 2020; 26(7): 1656-66.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2541] [PMID: 31772122]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2541] [PMID: 31772122]
[94]
Dong J, Zhu D, Tang X, et al. Detection of circulating tumor cell molecular subtype in pulmonary vein predicting prognosis of stage I–III non-small cell lung cancer patients. Front Oncol 2019; 9: 1139.
[http://dx.doi.org/10.3389/fonc.2019.01139] [PMID: 31737568]
[http://dx.doi.org/10.3389/fonc.2019.01139] [PMID: 31737568]
[95]
Bidard FC, Huguet F, Louvet C, et al. Circulating tumor cells in locally advanced pancreatic adenocarcinoma: The ancillary CirCe 07 study to the LAP 07 trial. Ann Oncol 2013; 24(8): 2057-61.
[http://dx.doi.org/10.1093/annonc/mdt176] [PMID: 23676420]
[http://dx.doi.org/10.1093/annonc/mdt176] [PMID: 23676420]
[96]
Okubo K, Uenosono Y, Arigami T, et al. Clinical impact of circulating tumor cells and therapy response in pancreatic cancer. Eur J Surg Oncol 2017; 43(6): 1050-5.
[http://dx.doi.org/10.1016/j.ejso.2017.01.241] [PMID: 28233633]
[http://dx.doi.org/10.1016/j.ejso.2017.01.241] [PMID: 28233633]
[97]
Wei T, Zhang X, Zhang Q, et al. Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer. Cancer Lett 2019; 452: 237-43.
[http://dx.doi.org/10.1016/j.canlet.2019.03.009] [PMID: 30905814]
[http://dx.doi.org/10.1016/j.canlet.2019.03.009] [PMID: 30905814]
[98]
Zhao XH, Wang ZR, Chen CL, et al. Molecular detection of epithelial-mesenchymal transition markers in circulating tumor cells from pancreatic cancer patients: Potential role in clinical practice. World J Gastroenterol 2019; 25(1): 138-50.
[http://dx.doi.org/10.3748/wjg.v25.i1.138] [PMID: 30643364]
[http://dx.doi.org/10.3748/wjg.v25.i1.138] [PMID: 30643364]
[99]
Zhu P, Liu HY, Liu FC, et al. Circulating tumor cells expressing Krüppel-like factor 8 and vimentin as predictors of poor prognosis in pancreatic cancer patients. Cancer Contr 2021; 28.
[http://dx.doi.org/10.1177/10732748211027163] [PMID: 34378430]
[http://dx.doi.org/10.1177/10732748211027163] [PMID: 34378430]
[100]
Goldkorn A, Ely B, Quinn DI, et al. Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol 2014; 32(11): 1136-42.
[http://dx.doi.org/10.1200/JCO.2013.51.7417] [PMID: 24616308]
[http://dx.doi.org/10.1200/JCO.2013.51.7417] [PMID: 24616308]
[101]
Goodman OB Jr, Fink LM, Symanowski JT, et al. Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors. Cancer Epidemiol Biomarkers Prev 2009; 18(6): 1904-13.
[http://dx.doi.org/10.1158/1055-9965.EPI-08-1173] [PMID: 19505924]
[http://dx.doi.org/10.1158/1055-9965.EPI-08-1173] [PMID: 19505924]
[102]
Chen J, Cao S, Situ B, et al. Metabolic reprogramming-based characterization of circulating tumor cells in prostate cancer. J Exp Clin Cancer Res 2018; 37(1): 127.
[http://dx.doi.org/10.1186/s13046-018-0789-0] [PMID: 29954422]
[http://dx.doi.org/10.1186/s13046-018-0789-0] [PMID: 29954422]
[103]
Sha MY, Xu H, Natan MJ, Cromer R. Surface-enhanced H scattering tags for rapid and homogeneous detection of circulating tumor cells in the presence of human whole blood. J Am Chem Soc 2008; 130(51): 17214-5.
[http://dx.doi.org/10.1021/ja804494m] [PMID: 19053187]
[http://dx.doi.org/10.1021/ja804494m] [PMID: 19053187]
[104]
Han SI, Han KH. Electrical detection method for circulating tumor cells using graphene nanoplates. Anal Chem 2015; 87(20): 10585-92.
[http://dx.doi.org/10.1021/acs.analchem.5b03147] [PMID: 26402053]
[http://dx.doi.org/10.1021/acs.analchem.5b03147] [PMID: 26402053]
[105]
Shen Z, Wu A, Chen X. Current detection technologies for circulating tumor cells. Chem Soc Rev 2017; 46(8): 2038-56.
[http://dx.doi.org/10.1039/C6CS00803H] [PMID: 28393954]
[http://dx.doi.org/10.1039/C6CS00803H] [PMID: 28393954]
[106]
Vona G, Sabile A, Louha M, et al. Isolation by size of epithelial tumor cells: A new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol 2000; 156(1): 57-63.
[http://dx.doi.org/10.1016/S0002-9440(10)64706-2] [PMID: 10623654]
[http://dx.doi.org/10.1016/S0002-9440(10)64706-2] [PMID: 10623654]
[107]
Pinzani P, Salvadori B, Simi L, et al. Isolation by size of epithelial tumor cells in peripheral blood of patients with breast cancer: Correlation with real-time reverse transcriptase–polymerase chain reaction results and feasibility of molecular analysis by laser microdissection. Hum Pathol 2006; 37(6): 711-8.
[http://dx.doi.org/10.1016/j.humpath.2006.01.026] [PMID: 16733212]
[http://dx.doi.org/10.1016/j.humpath.2006.01.026] [PMID: 16733212]
[108]
Zheng S, Lin HK, Lu B, et al. 3D microfilter device for viable Circulating Tumor Cell (CTC) enrichment from blood. Biomed Microdevices 2011; 13(1): 203-13.
[http://dx.doi.org/10.1007/s10544-010-9485-3] [PMID: 20978853]
[http://dx.doi.org/10.1007/s10544-010-9485-3] [PMID: 20978853]
[109]
Bhagat AAS, Hou HW, Li LD, Lim CT, Han J. Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation. Lab Chip 2011; 11(11): 1870-8.
[http://dx.doi.org/10.1039/c0lc00633e] [PMID: 21505682]
[http://dx.doi.org/10.1039/c0lc00633e] [PMID: 21505682]
[110]
Tan SJ, Lakshmi RL, Chen P, Lim WT, Yobas L, Lim CT. Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. Biosens Bioelectron 2010; 26(4): 1701-5.
[http://dx.doi.org/10.1016/j.bios.2010.07.054] [PMID: 20719496]
[http://dx.doi.org/10.1016/j.bios.2010.07.054] [PMID: 20719496]
[111]
Artandi SE, DePinho RA. Telomeres and telomerase in cancer. Carcinogenesis 2010; 31(1): 9-18.
[http://dx.doi.org/10.1093/carcin/bgp268] [PMID: 19887512]
[http://dx.doi.org/10.1093/carcin/bgp268] [PMID: 19887512]
[112]
Moon HS, Kwon K, Kim SI, et al. Continuous separation of breast cancer cells from blood samples using Multi-Orifice Flow Fractionation (MOFF) and Dielectrophoresis (DEP). Lab Chip 2011; 11(6): 1118-25.
[http://dx.doi.org/10.1039/c0lc00345j] [PMID: 21298159]
[http://dx.doi.org/10.1039/c0lc00345j] [PMID: 21298159]
[113]
Gascoyne PRC, Noshari J, Anderson TJ, Becker FF. Isolation of rare cells from cell mixtures by dielectrophoresis. Electrophoresis 2009; 30(8): 1388-98.
[http://dx.doi.org/10.1002/elps.200800373] [PMID: 19306266]
[http://dx.doi.org/10.1002/elps.200800373] [PMID: 19306266]
[114]
Sajay BNG, Chang CP, Ahmad H, et al. Microfluidic platform for negative enrichment of circulating tumor cells. Biomed Microdevices 2014; 16(4): 537-48.
[http://dx.doi.org/10.1007/s10544-014-9856-2] [PMID: 24668439]
[http://dx.doi.org/10.1007/s10544-014-9856-2] [PMID: 24668439]
[115]
Swennenhuis JF, Van Dalum G, Zeune LL, Terstappen LWMM. Improving the Cell Search® system. Expert Rev Mol Diagn 2016; 16(12): 1291-305.
[http://dx.doi.org/10.1080/14737159.2016.1255144] [PMID: 27797592]
[http://dx.doi.org/10.1080/14737159.2016.1255144] [PMID: 27797592]
[116]
Wang L, Balasubramanian P, Chen AP, Kummar S, Evrard YA, Kinders RJ. Promise and limits of the cell search platform for evaluating pharmacodynamics in circulating tumor cells. Semin Oncol 2016; 43(4): 464-75.
[http://dx.doi.org/10.1053/j.seminoncol.2016.06.004] [PMID: 27663478]
[http://dx.doi.org/10.1053/j.seminoncol.2016.06.004] [PMID: 27663478]
[117]
Miltenyi S, Müller W, Weichel W, Radbruch A. High gradient magnetic cell separation with MACS. Cytometry 1990; 11(2): 231-8.
[http://dx.doi.org/10.1002/cyto.990110203] [PMID: 1690625]
[http://dx.doi.org/10.1002/cyto.990110203] [PMID: 1690625]
[118]
Theil G, Boehm C, Fischer K, et al. In vivo isolation of circulating tumor cells in patients with different stages of prostate cancer. Oncol Lett 2021; 21(5): 357.
[http://dx.doi.org/10.3892/ol.2021.12618] [PMID: 33747214]
[http://dx.doi.org/10.3892/ol.2021.12618] [PMID: 33747214]
[119]
Cann GM, Gulzar ZG, Cooper S, et al. mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation of gene expression and pathways found in prostate cancer. PLoS One 2012; 7(11): e49144.
[http://dx.doi.org/10.1371/journal.pone.0049144] [PMID: 23145101]
[http://dx.doi.org/10.1371/journal.pone.0049144] [PMID: 23145101]
[120]
Danila DC, Samoila A, Patel C, et al. Clinical validity of detecting circulating tumor cells by AdnaTest assay compared with direct detection of tumor mRNA in stabilized whole blood, as a biomarker predicting overall survival for metastatic castration-resistant prostate cancer patients. Cancer J 2016; 22(5): 315-20.
[http://dx.doi.org/10.1097/PPO.0000000000000220] [PMID: 27749322]
[http://dx.doi.org/10.1097/PPO.0000000000000220] [PMID: 27749322]
[121]
Sequist LV, Nagrath S, Toner M, Haber DA, Lynch TJ. The CTC-chip: An exciting new tool to detect circulating tumor cells in lung cancer patients. J Thorac Oncol 2009; 4(3): 281-3.
[http://dx.doi.org/10.1097/JTO.0b013e3181989565] [PMID: 19247082]
[http://dx.doi.org/10.1097/JTO.0b013e3181989565] [PMID: 19247082]
[122]
Yoon HJ, Kim TH, Zhang Z, et al. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat Nanotechnol 2013; 8(10): 735-41.
[http://dx.doi.org/10.1038/nnano.2013.194] [PMID: 24077027]
[http://dx.doi.org/10.1038/nnano.2013.194] [PMID: 24077027]
[123]
Gleghorn JP, Pratt ED, Denning D, et al. Capture of circulating tumor cells from whole blood of prostate cancer patients using Geometrically Enhanced Differential Immunocapture (GEDI) and a prostate-specific antibody. Lab Chip 2010; 10(1): 27-9.
[http://dx.doi.org/10.1039/B917959C] [PMID: 20024046]
[http://dx.doi.org/10.1039/B917959C] [PMID: 20024046]
[124]
Harouaka RA, Zhou MD, Yeh YT, et al. Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells. Clin Chem 2014; 60(2): 323-33.
[http://dx.doi.org/10.1373/clinchem.2013.206805] [PMID: 24132944]
[http://dx.doi.org/10.1373/clinchem.2013.206805] [PMID: 24132944]
[125]
Zhou MD, Hao S, Williams AJ, et al. Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells. Sci Rep 2015; 5(1): 7967.
[http://dx.doi.org/10.1038/srep07967] [PMID: 25623175]
[http://dx.doi.org/10.1038/srep07967] [PMID: 25623175]
[126]
Kim TH, Lim M, Park J, et al. FAST: Size-selective, clog-free isolation of rare cancer cells from whole blood at a liquid–liquid interface. Anal Chem 2017; 89(2): 1155-62.
[http://dx.doi.org/10.1021/acs.analchem.6b03534] [PMID: 27958721]
[http://dx.doi.org/10.1021/acs.analchem.6b03534] [PMID: 27958721]
[127]
Kaifi JT, Kunkel M, Das A, et al. Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: A prospective trial with different detection techniques. Cancer Biol Ther 2015; 16(5): 699-708.
[http://dx.doi.org/10.1080/15384047.2015.1030556] [PMID: 25807199]
[http://dx.doi.org/10.1080/15384047.2015.1030556] [PMID: 25807199]
[128]
Campton DE, Ramirez AB, Nordberg JJ, et al. High-recovery visual identification and single-cell retrieval of circulating tumor cells for genomic analysis using a dual-technology platform integrated with automated immunofluorescence staining. BMC Cancer 2015; 15(1): 360.
[http://dx.doi.org/10.1186/s12885-015-1383-x] [PMID: 25944336]
[http://dx.doi.org/10.1186/s12885-015-1383-x] [PMID: 25944336]
[129]
Miller MC, Robinson PS, Wagner C, O’Shannessy DJ. The parsortix™ Cell separation system—A versatile liquid biopsy platform. Cytometry A 2018; 93(12): 1234-9.
[http://dx.doi.org/10.1002/cyto.a.23571] [PMID: 30107082]
[http://dx.doi.org/10.1002/cyto.a.23571] [PMID: 30107082]
[130]
Zhang P, Shi B, Gao H, et al. An EpCAM/CD3 bispecific antibody efficiently eliminates hepatocellular carcinoma cells with limited galectin-1 expression. Cancer Immunol Immunother 2014; 63(2): 121-32.
[http://dx.doi.org/10.1007/s00262-013-1497-4] [PMID: 24177984]
[http://dx.doi.org/10.1007/s00262-013-1497-4] [PMID: 24177984]
[131]
Xiao Z, Chung H, Banan B, et al. Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma. Cancer Lett 2015; 360(2): 302-9.
[http://dx.doi.org/10.1016/j.canlet.2015.02.036] [PMID: 25721088]
[http://dx.doi.org/10.1016/j.canlet.2015.02.036] [PMID: 25721088]
[132]
Münz M, Murr A, Kvesic M, et al. Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies. Cancer Cell Int 2010; 10(1): 44.
[http://dx.doi.org/10.1186/1475-2867-10-44] [PMID: 21044305]
[http://dx.doi.org/10.1186/1475-2867-10-44] [PMID: 21044305]
[133]
Wimberger P, Gilet H, Gonschior AK, et al. Deterioration in Quality of Life (QoL) in patients with malignant ascites: Results from a phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone. Ann Oncol 2012; 23(8): 1979-85.
[http://dx.doi.org/10.1093/annonc/mds178] [PMID: 22734013]
[http://dx.doi.org/10.1093/annonc/mds178] [PMID: 22734013]
[134]
Baumann K, Pfisterer J, Wimberger P, et al. Intraperitoneal treatment with the trifunctional bispecific antibody catumaxomab in patients with platinum-resistant epithelial ovarian cancer: A phase IIa study of the AGO Study Group. Gynecol Oncol 2011; 123(1): 27-32.
[http://dx.doi.org/10.1016/j.ygyno.2011.06.004] [PMID: 21733566]
[http://dx.doi.org/10.1016/j.ygyno.2011.06.004] [PMID: 21733566]
[135]
Heiss MM, Murawa P, Koralewski P, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial. Int J Cancer 2010; 127(9): 2209-21.
[http://dx.doi.org/10.1002/ijc.25423] [PMID: 20473913]
[http://dx.doi.org/10.1002/ijc.25423] [PMID: 20473913]
[136]
Burges A, Wimberger P, Kümper C, et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: A phase I/II study. Clin Cancer Res 2007; 13(13): 3899-905.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2769] [PMID: 17606723]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2769] [PMID: 17606723]
[137]
Heiss MM, Ströhlein MA, Jäger M, et al. Immunotherapy of malignant ascites with trifunctional antibodies. Int J Cancer 2005; 117(3): 435-43.
[http://dx.doi.org/10.1002/ijc.21165] [PMID: 15906359]
[http://dx.doi.org/10.1002/ijc.21165] [PMID: 15906359]
[138]
Marmé A, Strauß G, Bastert G, Grischke EM, Moldenhauer G. Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma. Int J Cancer 2002; 101(2): 183-9.
[http://dx.doi.org/10.1002/ijc.10562] [PMID: 12209996]
[http://dx.doi.org/10.1002/ijc.10562] [PMID: 12209996]
[139]
Huang J, Li C, Wang Y, et al. Cytokine-Induced Killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133high cancer stem cells in vitro and in vivo. Clin Immunol 2013; 149(1): 156-68.
[http://dx.doi.org/10.1016/j.clim.2013.07.006] [PMID: 23994769]
[http://dx.doi.org/10.1016/j.clim.2013.07.006] [PMID: 23994769]
[140]
Ma Z, He H, Sun F, et al. Selective targeted delivery of doxorubicin via conjugating to anti-CD24 antibody results in enhanced antitumor potency for hepatocellular carcinoma both in vitro and in vivo. J Cancer Res Clin Oncol 2017; 143(10): 1929-40.
[http://dx.doi.org/10.1007/s00432-017-2436-0] [PMID: 28536738]
[http://dx.doi.org/10.1007/s00432-017-2436-0] [PMID: 28536738]
[141]
Wang L, Su W, Liu Z, et al. CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma. Biomaterials 2012; 33(20): 5107-14.
[http://dx.doi.org/10.1016/j.biomaterials.2012.03.067] [PMID: 22494888]
[http://dx.doi.org/10.1016/j.biomaterials.2012.03.067] [PMID: 22494888]
[142]
Junttila MR, De Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 2013; 501(7467): 346-54.
[http://dx.doi.org/10.1038/nature12626] [PMID: 24048067]
[http://dx.doi.org/10.1038/nature12626] [PMID: 24048067]
[143]
Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19(11): 1423-37.
[http://dx.doi.org/10.1038/nm.3394] [PMID: 24202395]
[http://dx.doi.org/10.1038/nm.3394] [PMID: 24202395]
[144]
Bejarano L. Jordāo MJC, Joyce JA. Therapeutic targeting of the tumor microenvironment. Cancer Discov 2021; 11(4): 933-59.
[http://dx.doi.org/10.1158/2159-8290.CD-20-1808] [PMID: 33811125]
[http://dx.doi.org/10.1158/2159-8290.CD-20-1808] [PMID: 33811125]
[145]
Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci Transl Med 2016; 8(328): 328rv4.
[http://dx.doi.org/10.1126/scitranslmed.aad7118] [PMID: 26936508]
[http://dx.doi.org/10.1126/scitranslmed.aad7118] [PMID: 26936508]
[146]
Han C, Zhang A, Liu Z, Moore C, Fu YX. Small molecular drugs reshape tumor microenvironment to synergize with immunotherapy. Oncogene 2021; 40(5): 885-98.
[http://dx.doi.org/10.1038/s41388-020-01575-7] [PMID: 33288883]
[http://dx.doi.org/10.1038/s41388-020-01575-7] [PMID: 33288883]
[147]
Liu Z, Han C, Fu YX. Targeting innate sensing in the tumor microenvironment to improve immunotherapy. Cell Mol Immunol 2020; 17(1): 13-26.
[http://dx.doi.org/10.1038/s41423-019-0341-y] [PMID: 31844141]
[http://dx.doi.org/10.1038/s41423-019-0341-y] [PMID: 31844141]
[148]
Mender I, Gryaznov S, Dikmen ZG, Wright WE, Shay JW. Induction of telomere dysfunction mediated by the telomerase substrate precursor 6-thio-2′-deoxyguanosine. Cancer Discov 2015; 5(1): 82-95.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0609] [PMID: 25516420]
[http://dx.doi.org/10.1158/2159-8290.CD-14-0609] [PMID: 25516420]
[149]
Mender I, LaRanger R, Luitel K, et al. Telomerase-mediated strategy for overcoming non–small cell lung cancer targeted therapy and chemotherapy resistance. Neoplasia 2018; 20(8): 826-37.
[http://dx.doi.org/10.1016/j.neo.2018.06.002] [PMID: 30015158]
[http://dx.doi.org/10.1016/j.neo.2018.06.002] [PMID: 30015158]
[150]
Mender I, Zhang A, Ren Z, et al. Telomere stress potentiates sting dependent anti-tumor immunity. Cancer Cell 2020; 38(3): 400-11.
[http://dx.doi.org/10.1016/j.ccell.2020.05.020] [PMID: 32619407]
[http://dx.doi.org/10.1016/j.ccell.2020.05.020] [PMID: 32619407]
