miRNAs: micro-managers of anticancer combination therapies

Angiogenesis

Volumn 20, Issue 2, 2017, Pages 269-285

  van Beijnum, Judy R ^a   Giovannetti, Elisa ^a   Poel, Dennis ^a   Nowak Sliwinska, Patrycja ^b   Griffioen, Arjan W ^a  

^a University of Amsterdam   (Netherlands)

^b UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

AngiomRs; Anti angiogenic therapy; Chemotherapy; Combination therapy; MicroRNA; Nanocarriers; Photodynamic therapy; Radiotherapy; Tumor angiogenesis

Indexed keywords

ASPARAGINASE; CAPECITABINE; CHLOROTOXIN; DAUNORUBICIN; DEXAMETHASONE; DOXORUBICIN; ENTINOSTAT; FLUOROURACIL; GEMCITABINE; LEUCINE; MICRORNA; MICRORNA 145; MICRORNA 192; MICRORNA 34; NANOPARTICLE; PROTEIN INHIBITOR; RUBONE; SORAFENIB; SUNITINIB; TAMOXIFEN; TOPOTECAN; TRASTUZUMAB; UNCLASSIFIED DRUG; VINCRISTINE; ANTINEOPLASTIC AGENT; RNA;

ANTIANGIOGENIC ACTIVITY; ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; ANTISENSE THERAPY; CANCER INHIBITION; CANCER RADIOTHERAPY; CANCER THERAPY; CARCINOGENESIS; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG POTENTIATION; HUMAN; NONHUMAN; PHOTODYNAMIC THERAPY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW; SUBSTITUTION THERAPY; TREATMENT RESPONSE; ANIMAL; METABOLISM; NEOPLASM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; VASCULARIZATION;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; HUMANS; MICRORNAS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; RNA, NEOPLASM;

EID: 85018738338     PISSN: 09696970     EISSN: 15737209     Source Type: Journal    
DOI: 10.1007/s10456-017-9545-x     Document Type: Review

References (161)

1. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. doi:10.1016/j.cell.2011.02.013
2. Griffioen AW, Molema G (2000) Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev 52:237–268
3. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307. doi:10.1038/nature10144
4. Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med 17:1359–1370. doi:10.1038/nm.2537
5. van Beijnum JR, Nowak-Sliwinska P, Huijbers EJM et al (2015) The great escape; the hallmarks of resistance to antiangiogenic therapy. Pharmacol Rev 67:441–461. doi:10.1124/PR.114.010215
6. Huijbers EJM, van Beijnum JR, Thijssen VL et al (2016) Role of the tumor stroma in resistance to anti-angiogenic therapy. Drug Resist Updat 25:26–37. doi:10.1016/j.drup.2016.02.002
7. Gotink KJ, Broxterman HJ, Labots M et al (2011) Lysosomal sequestration of sunitinib: a novel mechanism of drug resistance. Clin Cancer Res 17:7337–7346. doi:10.1158/1078-0432.CCR-11-1667
8. Sethi S, Ali S, Sethi S, Sarkar FH (2014) MicroRNAs in personalized cancer therapy. Clin Genet 86:68–73. doi:10.1111/cge.12362
9. van Beijnum JR, Griffioen AW (2005) In silico analysis of angiogenesis associated gene expression identifies angiogenic stage related profiles. Biochim Biophys Acta—Rev Cancer 1755:121–134. doi:10.1016/j.bbcan.2005.06.001
10. van Beijnum JR, Dings RP, van der Linden E et al (2006) Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature. Blood 108:2339–2348. doi:10.1182/blood-2006-02-004291
11. Nanda A, St Croix B (2004) Tumor endothelial markers: new targets for cancer therapy. Curr Opin Oncol 16:44–49
12. Poliseno L, Tuccoli A, Mariani L et al (2006) MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108:3068–3071. doi:10.1182/blood-2006-01-012369
13. Wang S, Olson EN (2009) AngiomiRs—key regulators of angiogenesis. Curr Opin Genet Dev 19:205–211. doi:10.1016/j.gde.2009.04.002
14. Landskroner-Eiger S, Moneke I, Sessa WC (2013) miRNAs as modulators of angiogenesis. Cold Spring Harb Perspect Med 3:a006643. doi:10.1101/cshperspect.a006643
15. Suarez Y, Fernandez-Hernando C, Pober JS, Sessa WC (2007) Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res 100:1164–1173. doi:10.1161/01.RES.0000265065.26744.17
16. Heusschen R, van Gink M, Griffioen AW, Thijssen VL (2010) MicroRNAs in the tumor endothelium: novel controls on the angioregulatory switchboard. Biochim Biophys Acta 1805:87–96. doi:10.1016/j.bbcan.2009.09.005
17. Kuehbacher A, Urbich C, Dimmeler S (2008) Targeting microRNA expression to regulate angiogenesis. Trends Pharmacol Sci 29:12–15. doi:10.1016/j.tips.2007.10.014
18. Anand S, Cheresh DA (2011) MicroRNA-mediated regulation of the angiogenic switch. Curr Opin Hematol 18:171–176. doi:10.1097/MOH.0b013e328345a180
19. Gallach S, Calabuig-Fariñas S, Jantus-Lewintre E, Camps C (2014) MicroRNAs: promising new antiangiogenic targets in cancer. Biomed Res Int 2014:878450. doi:10.1155/2014/878450
20. Wu F, Yang Z, Li G (2009) Role of specific microRNAs for endothelial function and angiogenesis. Biochem Biophys Res Commun 386:549–553. doi:10.1016/j.bbrc.2009.06.075
21. Fish JE, Santoro MM, Morton SU et al (2008) miR-126 regulates Angiogenic signaling and vascular integrity. Dev Cell 15:272–284. doi:10.1016/j.devcel.2008.07.008
22. Wang S, Aurora AB, Johnson BA et al (2008) The endothelial-specific microrna miR-126 governs vascular integrity and angiogenesis. Dev Cell 15:261–271. doi:10.1016/j.devcel.2008.07.002
23. Kuhnert F, Mancuso MR, Hampton J et al (2008) Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development 135:3989–3993. doi:10.1242/dev.029736
24. Png KJ, Halberg N, Yoshida M, Tavazoie SF (2011) A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 481:190–194. doi:10.1038/nature10661
25. Würdinger T, Tannous BA, Saydam O et al (2008) miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 14:382–393. doi:10.1016/j.ccr.2008.10.005
26. Liu X-Q, Song W-J, Sun T-M et al (2011) Targeted delivery of antisense inhibitor of miRNA for antiangiogenesis therapy using cRGD-functionalized nanoparticles. Mol Pharm 8:250–259. doi:10.1021/mp100315q
27. Feng J, Huang T, Huang Q et al (2015) Pro-angiogenic microRNA-296 upregulates vascular endothelial growth factor and downregulates notch1 following cerebral ischemic injury. Mol Med Rep 12:8141–8147. doi:10.3892/mmr.2015.4436
28. Li Y, Song Y-H, Li F et al (2009) microRNA-221 regulates high glucose-induced endothelial dysfunction. Biochem Biophys Res Commun 381:81–83. doi:10.1016/j.bbrc.2009.02.013
29. Hua Z, Lv Q, Ye W et al (2006) MiRNA-directed regulation of vegf and other angiogenic factors under hypoxia. PLoS ONE 1:e116. doi:10.1371/journal.pone.0000116
30. Dai X, Tan C (2015) Combination of microRNA therapeutics with small-molecule anticancer drugs: mechanism of action and co-delivery nanocarriers. Adv Drug Deliv Rev 81:184–197. doi:10.1016/j.addr.2014.09.010
31. Shi Z, Chen Q, Li C et al (2014) MiR-124 governs glioma growth and angiogenesis and enhances chemosensitivity by targeting R-Ras and N-Ras. Neuro Oncol 16:1341–1353. doi:10.1093/neuonc/nou084
32. Cascio S, D’Andrea A, Ferla R et al (2010) miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol 224:242–249. doi:10.1002/jcp.22126
33. Kong W, He L, Richards EJ et al (2014) Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer. Oncogene 33:679–689. doi:10.1038/onc.2012.636
34. Liu L-Z, Li C, Chen Q et al (2011) MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS ONE 6:e19139. doi:10.1371/journal.pone.0019139
35. Polytarchou C, Iliopoulos D, Hatziapostolou M et al (2011) Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Res 71:4720–4731. doi:10.1158/0008-5472.CAN-11-0365
36. Babae N, Bourajjaj M, Liu Y et al (2014) Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma. Oncotarget 5:6687–6700. doi:10.18632/oncotarget.2235
37. Nowak-Sliwinska P, Segura T, Iruela-Arispe ML (2014) The chicken chorioallantoic membrane model in biology, medicine and bioengineering. Angiogenesis 17:779–804. doi:10.1007/s10456-014-9440-7
38. Chan YC, Khanna S, Roy S, Sen CK (2011) miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J Biol Chem 286:2047–2056. doi:10.1074/jbc.M110.158790
39. Shi L, Zhang S, Wu H et al (2013) MiR-200c Increases the radiosensitivity of non-small-cell lung cancer cell line A549 by targeting VEGF-VEGFR2 pathway. PLoS ONE 8:e78344. doi:10.1371/journal.pone.0078344
40. Anand S, Majeti BK, Acevedo LM et al (2010) MicroRNA-132–mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med 16:909–914. doi:10.1038/nm.2186
41. Ling H, Fabbri M, Calin GA (2013) MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 12:847–865. doi:10.1038/nrd4140
42. M Mk, Goyal R (2016) LncRNA as a therapeutic target for angiogenesis. Curr Top Med Chem. https://www.ncbi.nlm.nih.gov/pubmed/27848894
43. Jia P, Cai H, Liu X et al (2016) Long non-coding RNA H19 regulates glioma angiogenesis and the biological behavior of glioma-associated endothelial cells by inhibiting microRNA-29a. Cancer Lett 381:359–369. doi:10.1016/j.canlet.2016.08.009
44. Gandhi NS, Tekade RK, Chougule MB (2014) Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: current progress and advances. J Control Releas 194:238–256. doi:10.1016/j.jconrel.2014.09.001
45. Williams M, Cheng YY, Blenkiron C, Reid G (2016) Exploring mechanisms of microRNA downregulation in cancer. MicroRNA (Shariqah, United Arab Emirates). https://www.ncbi.nlm.nih.gov/pubmed/27928946
46. Bader AG, Brown D, Winkler M (2010) The promise of microRNA replacement therapy. Cancer Res 70:7027–7030. doi:10.1158/0008-5472.CAN-10-2010
47. Li Z, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13:622–638. doi:10.1038/nrd4359
48. Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222. doi:10.1038/nrd.2016.246
49. van Rooij E, Kauppinen S (2014) Development of microRNA therapeutics is coming of age. EMBO Mol Med 6:851–864. doi:10.15252/emmm.201100899
50. Soriano A, París-Coderch L, Jubierre L et al (2016) MicroRNA-497 impairs the growth of chemoresistant neuroblastoma cells by targeting cell cycle, survival and vascular permeability genes. Oncotarget 7:9271–9287. doi:10.18632/oncotarget.7005
51. Cheng CJ, Bahal R, Babar IA et al (2014) MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 518:107–110. doi:10.1038/nature13905
52. Würdinger T, Tannous BA (2009) Glioma angiogenesis: towards novel RNA therapeutics. Cell Adhes Migr 3:230–235. doi:10.4161/cam.3.2.7910
53. Simonson B, Das S (2015) MicroRNA therapeutics: the next magic bullet? Mini Rev Med Chem 15:467–474
54. Chen L, Zhang K, Shi Z et al (2014) A lentivirus-mediated miR-23b sponge diminishes the malignant phenotype of glioma cells in vitro and in vivo. Oncol Rep 31:1573–1580. doi:10.3892/or.2014.3012
55. Li X, Su Y, Sun B et al (2016) An artificially designed interfering lncRNA expressed by oncolytic adenovirus competitively consumes oncomiRs to exert antitumor efficacy in hepatocellular carcinoma. Mol Cancer Ther 15:1436–1451. doi:10.1158/1535-7163.MCT-16-0096
56. Su Y, Sun B, Lin X et al (2014) Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma. Oncotarget 7:49143–49155. doi:10.18632/oncotarget.9237
57. Xiao Z, Chen Y (2017) Identification of small molecule modulators of microRNA by library screening. Method Mol Biol. https://www.ncbi.nlm.nih.gov/pubmed/27924482
58. Gumireddy K, Young DD, Xiong X et al (2008) Small-molecule inhibitors of microRNA miR-21 function. Angew Chemie Int Ed 47:7482–7484. doi:10.1002/anie.200801555
59. Velagapudi SP, Cameron MD, Haga CL et al (2016) Design of a small molecule against an oncogenic noncoding RNA. Proc Natl Acad Sci USA 113:5898–5903. doi:10.1073/pnas.1523975113
60. Xiao Z, Li CH, Chan SL et al (2014) A small-molecule modulator of the tumor-suppressor miR34a inhibits the growth of hepatocellular carcinoma. Cancer Res 74:6236–6247. doi:10.1158/0008-5472.CAN-14-0855
61. Lee S-Y, Lee S, Choi E et al (2016) Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury. Sci Rep 6:23472. doi:10.1038/srep23472
62. Dowdy SF (2017) Overcoming cellular barriers for RNA therapeutics. Nat Biotechnol. doi:10.1038/nbt.3802
63. Nair JK, Willoughby JLS, Chan A et al (2014) Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc 136:16958–16961. doi:10.1021/ja505986a
64. Reid G, Kao SC, Pavlakis N et al (2016) Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. Epigenomics 8:1079–1085. doi:10.2217/epi-2016-0035
65. Yousefi A, Bourajjaj M, Babae N et al (2014) Anginex lipoplexes for delivery of anti-angiogenic siRNA. Int J Pharm 472:175–184. doi:10.1016/j.ijpharm.2014.06.028
66. Beg MS, Brenner AJ, Sachdev J et al (2016) Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest New Drugs. doi:10.1007/s10637-016-0407-y
67. Arunachalam G, Lakshmanan AP, Samuel SM et al (2016) Molecular interplay between microRNA-34a and Sirtuin1 in hyperglycemia-mediated impaired angiogenesis in endothelial cells: effects of metformin. J Pharmacol Exp Ther 356:314–323. doi:10.1124/jpet.115.226894
68. Zhao Y, Tu M-J, Yu Y-F et al (2015) Combination therapy with bioengineered miR-34a prodrug and doxorubicin synergistically suppresses osteosarcoma growth. Biochem Pharmacol 98:602–613. doi:10.1016/j.bcp.2015.10.015
69. Yu G, Yao W, Xiao W et al (2014) MicroRNA-34a functions as an anti-metastatic microRNA and suppresses angiogenesis in bladder cancer by directly targeting CD44. J Exp Clin Cancer Res 33:779. doi:10.1186/s13046-014-0115-4
70. Yang F, Li Q, Gong Z et al (2013) MicroRNA-34a targets Bcl-2 and sensitizes human hepatocellular carcinoma cells to sorafenib treatment. Technol Cancer Res Treat 13:77–86. doi:10.7785/tcrt.2012.500364
71. Costa PM, Cardoso AL, Custódia C et al (2015) MiRNA-21 silencing mediated by tumor-targeted nanoparticles combined with sunitinib: a new multimodal gene therapy approach for glioblastoma. J Control Release 207:31–39. doi:10.1016/j.jconrel.2015.04.002
72. Costa PM, Cardoso AL, Nóbrega C et al (2013) MicroRNA-21 silencing enhances the cytotoxic effect of the antiangiogenic drug sunitinib in glioblastoma. Hum Mol Genet 22:904–918. doi:10.1093/hmg/dds496
73. Passadouro M, Pedroso de Lima MC, Faneca H (2014) MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer. Int J Nanomedicine 9:3203–3217. doi:10.2147/IJN.S64456
74. Liu H, Liu Z, Jiang B et al (2015) Synthetic miR-145 mimic enhances the cytotoxic effect of the antiangiogenic drug sunitinib in glioblastoma. Cell Biochem Biophys 72:551–557. doi:10.1007/s12013-014-0501-8
75. Gotink KJ, Verheul HMW (2010) Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis 13:1–14. doi:10.1007/s10456-009-9160-6
76. Thijssen V, Postel R, Brandwijk R (2006) Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci USA. https://www.ncbi.nlm.nih.gov/pubmed/17043243
77. Wu SY, Rupaimoole R, Shen F et al (2016) A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer. Nat Commun 7:11169. doi:10.1038/ncomms11169
78. Lee SH, Jung YD, Choi YS, Lee YM (2015) Targeting of RUNX3 by miR-130a and miR-495 cooperatively increases cell proliferation and tumor angiogenesis in gastric cancer cells. Oncotarget 6:33269–33278. doi:10.18632/oncotarget.5037
79. Pihlmann M, Askou AL, Aagaard L et al (2012) Adeno-associated virus-delivered polycistronic microRNA-clusters for knockdown of vascular endothelial growth factor in vivo. J Gene Med 14:328–338. doi:10.1002/jgm.2623
80. Askou AL, Aagaard L, Kostic C et al (2015) Multigenic lentiviral vectors for combined and tissue-specific expression of miRNA—and protein-based antiangiogenic factors. Mol Ther Methods Clin Dev 2:14064. doi:10.1038/mtm.2014.64
81. Khella HWZ, Butz H, Ding Q et al (2015) miR-221/222 are involved in response to sunitinib treatment in metastatic renal cell carcinoma. Mol Ther 23:1748–1758. doi:10.1038/mt.2015.129
82. García-Donas J, Beuselinck B, Inglada-Pérez L et al (2016) Deep sequencing reveals microRNAs predictive of antiangiogenic drug response. JCI Insight 1:e86051. doi:10.1172/jci.insight.86051
83. Griffioen AW, Mans LA, de Graaf AMA et al (2012) Rapid angiogenesis onset after discontinuation of sunitinib treatment of renal cell carcinoma patients. Clin Cancer Res 18:3961–3971. doi:10.1158/1078-0432.CCR-12-0002
84. Goto Y, Kurozumi A, Nohata N et al (2016) The microRNA signature of patients with sunitinib failure: regulation of UHRF1 pathways by microRNA-101 in renal cell carcinoma. Oncotarget 7:59070–59086. doi:10.18632/oncotarget.10887
85. Merhautova J, Hezova R, Poprach A et al (2015) MiR-155 and miR-484 are associated with time to progression in metastatic renal cell carcinoma treated with sunitinib. Biomed Res Int 2015:941980. doi:10.1155/2015/941980
86. Prior C, Perez-Gracia JL, Garcia-Donas J et al (2014) Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma. PLoS ONE 9:e86263. doi:10.1371/journal.pone.0086263
87. Berkers J, Govaere O, Wolter P et al (2013) A possible role for microRNA-141 down-regulation in sunitinib resistant metastatic clear cell renal cell carcinoma through induction of epithelial-to-mesenchymal transition and hypoxia resistance. J Urol 189:1930–1938. doi:10.1016/j.juro.2012.11.133
88. Gámez-Pozo A, Antón-Aparicio LM, Bayona C et al (2012) MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients. Neoplasia 14:1144–1152
89. Shivapurkar N, Mikhail S, Navarro R et al (2013) Decrease in blood miR-296 predicts chemotherapy resistance and poor clinical outcome in patients receiving systemic chemotherapy for metastatic colon cancer. Int J Colorectal Dis 28:887. doi:10.1007/s00384-012-1560-1
90. Fojo T (2007) Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. Drug Resist Updat 10:59–67. doi:10.1016/j.drup.2007.02.002
91. Blower PE, Chung J-H, Verducci JS et al (2008) MicroRNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther 7:1–9. doi:10.1158/1535-7163.MCT-07-0573
92. Shi L, Chen J, Yang J et al (2010) MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res 1352:255–264. doi:10.1016/j.brainres.2010.07.009
93. Li W-Q, Yu H-Y, Li Y-M et al (2014) Higher LRRFIP1 expression in glioblastoma multiforme is associated with better response to teniposide, a type II topoisomerase inhibitor. Biochem Biophys Res Commun 446:1261–1267. doi:10.1016/j.bbrc.2014.03.105
94. Si M-L, Zhu S, Wu H et al (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803. doi:10.1038/sj.onc.1210083
95. De Mattos-Arruda L, Bottai G, Nuciforo PG et al (2015) MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget 6:37269–37280. doi:10.18632/oncotarget.5495
96. Hwang J-H, Voortman J, Giovannetti E et al (2010) Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLoS ONE 5:e10630. doi:10.1371/journal.pone.0010630
97. Jamieson NB, Morran DC, Morton JP et al (2012) MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. Clin Cancer Res 18:534–545. doi:10.1158/1078-0432.CCR-11-0679
98. Frampton AE, Castellano L, Colombo T et al (2014) MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression. Gastroenterology 146(268–77):e18. doi:10.1053/j.gastro.2013.10.010
99. Mei Y, Gao C, Wang K et al (2014) Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia. Cancer Sci 105:463–472. doi:10.1111/cas.12370
100. Lee D, Sun S, Zhang XQ et al (2015) MicroRNA-210 and endoplasmic reticulum chaperones in the regulation of chemoresistance in glioblastoma. J Cancer 6:227–232. doi:10.7150/jca.10765
101. Nicoli S, Standley C, Walker P et al (2010) MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature 464:1196–1200. doi:10.1038/nature08889
102. Zhu X, Li H, Long L et al (2012) miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A. Acta Biochim Biophys Sin (Shanghai) 44:519–526. doi:10.1093/abbs/gms026
103. Saito Y, Friedman JM, Chihara Y et al (2009) Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells. Biochem Biophys Res Commun 379:726–731. doi:10.1016/j.bbrc.2008.12.098
104. Berndsen RH, Abdul UK, Weiss A et al (2017) Epigenetic approach for angiostatic therapy: promising combinations for cancer treatment. Angiogenesis. doi:10.1007/s10456-017-9551-z
105. Wang S, Zhu L, Zuo W et al (2016) MicroRNA-mediated epigenetic targeting of Survivin significantly enhances the antitumor activity of paclitaxel against non-small cell lung cancer. Oncotarget 7:37693–37713. doi:10.18632/oncotarget.9264
106. Bi C, Chung T-H, Huang G et al (2015) Genome-wide pharmacologic unmasking identifies tumor suppressive microRNAs in multiple myeloma. Oncotarget 6:26508–26518. doi:10.18632/oncotarget.4769
107. Zhao J, Fu W, Liao H et al (2015) The regulatory and predictive functions of miR-17 and miR-92 families on cisplatin resistance of non-small cell lung cancer. BMC Cancer 15:731. doi:10.1186/s12885-015-1713-z
108. Zhao H-Y, Ooyama A, Yamamoto M et al (2008) Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in human colon cancer KM12C cells. Cancer Lett 270:156–163. doi:10.1016/j.canlet.2008.04.045
109. Pineau P, Volinia S, McJunkin K et al (2010) miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci USA 107:264–269. doi:10.1073/pnas.0907904107
110. Chen L, Zhang J, Han L et al (2012) Downregulation of miR-221/222 sensitizes glioma cells to temozolomide by regulating apoptosis independently of p53 status. Oncol Rep 27:854–860. doi:10.3892/or.2011.1535
111. Ye Z, Hao R, Cai Y et al (2016) Knockdown of miR-221 promotes the cisplatin-inducing apoptosis by targeting the BIM-Bax/Bak axis in breast cancer. Tumour Biol 37:4509–4515. doi:10.1007/s13277-015-4267-4
112. Park J-K, Lee EJ, Esau C, Schmittgen TD (2009) Antisense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas 38:e190–e199. doi:10.1097/MPA.0b013e3181ba82e1
113. Gan R, Yang Y, Yang X et al (2014) Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3. Cancer Gene Ther 21:290–296. doi:10.1038/cgt.2014.29
114. Chen D, Yan W, Liu Z et al (2016) Downregulation of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression. Biomed Pharmacother 77:72–78. doi:10.1016/j.biopha.2015.12.002
115. Qi JH, Anand-Apte B (2015) Tissue inhibitor of metalloproteinase-3 (TIMP3) promotes endothelial apoptosis via a caspase-independent mechanism. Apoptosis 20:523–534. doi:10.1007/s10495-014-1076-y
116. Schaake-Koning C, van den Bogaert W, Dalesio O et al (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med 326:524–530. doi:10.1056/NEJM199202203260805
117. Chinot OL, Wick W, Mason W et al (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722. doi:10.1056/NEJMoa1308345
118. Forastiere AA, Goepfert H, Maor M et al (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349:2091–2098. doi:10.1056/NEJMoa031317
119. Overgaard J (2007) Hypoxic radiosensitization: adored and ignored. J Clin Oncol 25:4066–4074. doi:10.1200/JCO.2007.12.7878
120. Curtin NJ (2012) DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 12:801–817. doi:10.1038/nrc3399
121. West C, Davidson S, Roberts S, Hunter R (1993) Intrinsic radiosensitivity and prediction of patient response to radiotherapy for carcinoma of the cervix. Br J Cancer 68:819–823. doi:10.1038/bjc.1993.434
122. Kleibeuker EA, Fokas E, Allen PD et al (2016) Low dose angiostatic treatment counteracts radiotherapy-induced tumor perfusion and enhances the anti-tumor effect. Oncotarget 7:76613–76627. doi:10.18632/oncotarget.12814
123. Kleibeuker EA, Griffioen AW, Verheul HM et al (2012) Combining angiogenesis inhibition and radiotherapy: a double-edged sword. Drug Resist Updat 15:173–182. doi:10.1016/j.drup.2012.04.002
124. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62. doi:10.1126/science.1104819
125. Dings RPM, Loren M, Heun H et al (2007) Scheduling of radiation with angiogenesis inhibitors anginex and avastin improves therapeutic outcome via vessel normalization. Clin Cancer Res 13:3395–3402. doi:10.1158/1078-0432.CCR-06-2441
126. Hamming LC, Slotman BJ, Verheul HMW, Thijssen VL (2017) The clinical application of angiostatic therapy in combination with radiotherapy: past, present, future. Angiogenesis. doi:10.1007/s10456-017-9546-9
127. Begg AC, Stewart FA, Vens C (2011) Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 11:239–253. doi:10.1038/nrc3007
128. Kulshreshtha R, Ferracin M, Wojcik SE et al (2007) A microRNA signature of hypoxia. Mol Cell Biol 27:1859–1867. doi:10.1128/MCB.01395-06
129. Fasanaro P, D’Alessandra Y, Di Stefano V et al (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283:15878–15883. doi:10.1074/jbc.M800731200
130. Camps C, Buffa FM, Colella S et al (2008) hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 14:1340–1348. doi:10.1158/1078-0432.CCR-07-1755
131. Grosso S, Doyen J, Parks SK et al (2013) MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. Cell Death Dis 4:e544. doi:10.1038/cddis.2013.71
132. Yang W, Sun T, Cao J et al (2012) Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro. Exp Cell Res 318:944–954. doi:10.1016/j.yexcr.2012.02.010
133. Lou Y-L, Guo F, Liu F et al (2012) miR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia. Mol Cell Biochem 370:45–51. doi:10.1007/s11010-012-1396-6
134. Yang W, Wei J, Sun T, Liu F (2013) Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice. Radiat Oncol 8:102. doi:10.1186/1748-717X-8-102
135. Yang W, Wei J, Guo T et al (2014) Knockdown of miR-210 decreases hypoxic glioma stem cells stemness and radioresistance. Exp Cell Res 326:22–35. doi:10.1016/j.yexcr.2014.05.022
136. Yang D, Wang J, Xiao M et al (2016) Role of Mir-155 in controlling HIF-1α level and promoting endothelial cell maturation. Sci Rep 6:35316. doi:10.1038/srep35316
137. Robertson ED, Wasylyk C, Ye T et al (2014) The oncogenic microRNA Hsa-miR-155-5p targets the transcription factor ELK3 and links it to the hypoxia response. PLoS ONE 9:e113050. doi:10.1371/journal.pone.0113050
138. Babar IA, Czochor J, Steinmetz A et al (2011) Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells. Cancer Biol Ther 12:908–914. doi:10.4161/cbt.12.10.17681
139. Wang Y, Sun L (2016) Knockdown of LMP1-induced miR-155 sensitizes nasopharyngeal carcinoma cells to radiotherapy in vitro. Oncol Lett 11:3451–3456. doi:10.3892/ol.2016.4400
140. Gasparini P, Lovat F, Fassan M et al (2014) Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation. Proc Natl Acad Sci 111:4536–4541. doi:10.1073/pnas.1402604111
141. Cortez MA, Valdecanas D, Zhang X et al (2014) Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer. Mol Ther 22:1494–1503. doi:10.1038/mt.2014.79
142. Cortez MA, Valdecanas D, Niknam S et al (2015) In vivo delivery of miR-34a sensitizes lung tumors to radiation through RAD51 regulation. Mol Ther Nucleic Acids 4:e270. doi:10.1038/mtna.2015.47
143. Ma W, Ma C, Zhou N et al (2016) Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy. Sci Rep 6:31651. doi:10.1038/srep31651
144. Agostinis P, Berg K, Cengel KA et al (2011) Photodynamic therapy of cancer: an update. CA Cancer J Clin 61:250–281. doi:10.3322/caac.20114
145. Lim SH, Nowak-Sliwinska P, Kamarulzaman FA et al (2010) The neovessel occlusion efficacy of 15-hydroxypurpurin-7-lactone dimethyl ester induced with photodynamic therapy. Photochem Photobiol 86:397–402. doi:10.1111/j.1751-1097.2009.00684.x
146. Babilas P, Schreml S, Landthaler M, Szeimies R-M (2010) Photodynamic therapy in dermatology: state-of-the-art. Photodermatol Photoimmunol Photomed 26:118–132. doi:10.1111/j.1600-0781.2010.00507.x
147. Allison RR, Downie GH, Cuenca R et al (2004) Photosensitizers in clinical PDT. Photodiagnosis Photodyn Ther 1:27–42. doi:10.1016/S1572-1000(04)00007-9
148. Rumie Vittar NB, Lamberti MJ, Pansa MF et al (2013) Ecological photodynamic therapy: new trend to disrupt the intricate networks within tumor ecosystem. Biochim Biophys Acta 1835:86–99. doi:10.1016/j.bbcan.2012.10.004
149. Nowak-Sliwinska P, van Beijnum JR, van Berkel M et al (2010) Vascular regrowth following photodynamic therapy in the chicken embryo chorioallantoic membrane. Angiogenesis 13:281–292. doi:10.1007/s10456-010-9185-x
150. Weiss A, Ding X, van Beijnum JR et al (2015) Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer. Angiogenesis 18:233–244. doi:10.1007/s10456-015-9462-9
151. Griffioen AW, Weiss A, Berndsen RH et al (2014) The emerging quest for the optimal angiostatic combination therapy. Biochem Soc Trans 42:1608–1615. doi:10.1042/BST20140193
152. Weiss A, Den Bergh H, van Griffioen AW, Nowak-Sliwinska P (2012) Angiogenesis inhibition for the improvement of photodynamic therapy: the revival of a promising idea. Biochim Biophys Acta Rev Cancer 1826:53–70. doi:10.1016/j.bbcan.2012.03.003
153. Casas A, Di Venosa G, Hasan T, Batlle Al (2011) Mechanisms of resistance to photodynamic therapy. Curr Med Chem 18:2486–2515
154. Bach D, Fuereder J, Karbiener M et al (2013) Comprehensive analysis of alterations in the miRNome in response to photodynamic treatment. J Photochem Photobiol B 120:74–81. doi:10.1016/j.jphotobiol.2013.01.012
155. Kushibiki T (2010) Photodynamic therapy induces microRNA-210 and -296 expression in HeLa cells. J Biophotonics 3:368–372. doi:10.1002/jbio.200900082
156. Nowak-Sliwinska P, Weiss A, van Beijnum JR et al (2012) Angiostatic kinase inhibitors to sustain photodynamic angio-occlusion. J Cell Mol Med 16:1553–1562. doi:10.1111/j.1582-4934.2011.01440.x
157. Chakrabarti M, Banik NL, Ray SK (2013) Photofrin based photodynamic therapy and miR-99a transfection inhibited FGFR3 and PI3 K/Akt signaling mechanisms to control growth of human glioblastoma In vitro and in vivo. PLoS ONE 8:e55652. doi:10.1371/journal.pone.0055652
158. Kuusk T, Albiges L, Escudier B et al (2017) Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer. Angiogenesis. doi:10.1007/s10456-017-9550-0
159. Ramjiawan RR, Griffioen AW, Duda DG (2017) Anti-angiogenesis for cancer revisited: is there a role for combinations with immunotherapy? Angiogenesis. doi:10.1007/s10456-017-9552-y
160. Nowak-Sliwinska P, Weiss A, Ding X et al (2016) Optimization of drug combinations using feedback system control. Nat Protoc 11:302–315. doi:10.1038/nprot.2016.017
161. Weiss A, Nowak-Sliwinska P (2016) Current trends in multidrug optimization. J Lab Autom. doi:10.1177/2472630316682338