Molecular mechanisms of drug resistance of glioblastoma part 1: ABC family proteins and inhibitors

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Abstract

The most common high-grade brain tumor in the adult population is glioblastoma. The life expectancy of patients with this tumor does not exceed 12-15 months, while relapses are observed in 100% of cases. One of the main reasons for the low efficiency of glioblastoma therapy is its multidrug resistance. In the development of the latter, transporter proteins of the ABC family play a key role. In this part, the emphasis is on the search for new molecular targets among growth factors, their receptors, signal transduction kinases, microRNAs, transcription factors, protooncogenes, and tumor suppressor genes involved in the regulation of proteins and genes of the ABC family and associated with the development of multidrug resistance in glioblastoma cells. The review also discusses the mechanisms of the cytotoxic action of inhibitors: ABC family proteins, tyrosine kinase receptors, non-receptor tyrosine kinases, vascular endothelial growth factor, kinases of signaling cascades, transcription factors, histone deacetylases, methyltransferases, replication and synthesis of DNA, microtubules and proteasome used in glioblastoma therapy or undergoing clinical trials.

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About the authors

Alexander N. Chernov

Institute of Experimental Medicine

Author for correspondence.
Email: al.chernov@mail.ru
ORCID iD: 0000-0003-2464-7370
Scopus Author ID: 26649406700

Research Associate, Department of General Pathology and Pathological Physiology

Russian Federation, 12, Academician Pavlov Str., Saint Petersburg, 197376

Olga V. Shamova

Institute of Experimental Medicine; Saint Petersburg State University

Email: oshamova@yandex.ru
ORCID iD: 0000-0002-5168-2801
Scopus Author ID: 6603643804
ResearcherId: F-6743-2013

Dr. Sci. (Biol.), Associate Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of General Pathology and Pathological Physiology

Russian Federation, 12, Academician Pavlov Str., Saint Petersburg, 197376; Saint Petersburg

References

  1. Hanif F, Muzaffar K, Perveen K, et al. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev. 2017;18(1):3–9. doi: 10.22034/APJCP.2017.18.1.3
  2. Merabishvili VM. Oncological statistics (traditional methods, new information technologies): Guidelines for physicians. Part I. Saint Petersburg: Costa; 2015. (In Russ.)
  3. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi: 10.1056/NEJMoa043330
  4. Johnson DR, O’Neill BP. Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol. 2012;107(2):359–364. doi: 10.1007/s11060-011-0749-4
  5. Dréan A, Rosenberg S, Lejeune FX, et al. ATP binding cassette (ABC) transporters: expression and clinical value in glioblastoma. J Neurooncol. 2018;138(3):479–486. doi: 10.1007/s11060-018-2819-3
  6. Demina EP, Miroshnikova VV, Schwarzman AL. Role of the ABC transporters A1 and G1, key reverse cholesterol transport proteins, in atherosclerosis. Mol Biol (Mosk). 2016;50(2):223–230. doi: 10.7868/S002689841602004X
  7. Zolnerciks JK, Andress EJ, Nicolaou M, Linton KJ. Structure of ABC transporters. Essays Biochem. 2011;50(1):43–61. doi: 10.1042/bse0500043
  8. Gomez-Zepeda D, Taghi M, Scherrmann JM. ABC transporters at the blood-brain interfaces, their study models, and drug delivery implications in gliomas. Pharmaceutics. 2019;12(1):20. doi: 10.3390/pharmaceutics12010020
  9. Liu X. ABC Family Transporters. Adv Exp Med Biol. 2019;1141:13–100. doi: 10.1007/978-981-13-7647-4_2
  10. Cascorbi I, Haenisch S. Pharmacogenetics of ATP-binding cassette transporters and clinical implications. Methods Mol Biol. 2010;596:95–121. doi: 10.1007/978-1-60761-416-6_6
  11. Bhatia P, Bernier M, Sanghvi M, et al. Breast cancer resistance protein (BCRP/ABCG2) localises to the nucleus in glioblastoma multiforme cells. Xenobiotica. 2012;42(8):748–755. doi: 10.3109/00498254.2012.662726
  12. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11(7):1156–1166. doi: 10.1101/gr.184901
  13. Hientz K, Mohr A, Bhakta-Guha D, Efferth T. The role of p53 in cancer drug resistance and targeted chemotherapy. Oncotarget. 2017;8(5):8921–8946. doi: 10.18632/oncotarget.13475
  14. Zhang P, de Gooijer MC, Buil LCM, et al. ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2-Inhibitors. Int J Cancer. 2015;137(8):2007–2018. doi: 10.1002/ijc.29566
  15. Colardo M, Segatto M, Di Bartolomeo S. Targeting RTK-PI3K-mTOR axis in gliomas: an update. Int J Mol Sci. 2021;22(9):4899. doi: 10.3390/ijms22094899
  16. Latour M, Her N-G, Kesari S, Nurmemmedov E. WNT Signaling as a therapeutic target for glioblastoma. Int J Mol Sci. 2021;22(16):8428. doi: 10.3390/ijms22168428
  17. Healy FM, Prior IA, MacEwan DJ. The importance of Ras in drug resistance in cancer. Br J Pharmacol. 2021. doi: 10.1111/bph.15420
  18. Avci NG, Ebrahimzadeh-Pustchi S, Akay YM, et al. NF-κB inhibitor with temozolomide results in significant apoptosis in glioblastoma via the NF-κB(p65) and actin cytoskeleton regulatory pathways. Sci Rep. 2020;10(1):13352. doi: 10.1038/s41598-020-70392-5
  19. Xu P, Zhang G, Hou S, Sha LG. MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway. Biomed Pharmacother. 2018;106:1419–1427. doi: 10.1016/j.biopha.2018.06.084
  20. Chen X, Hao A, Li X, et al. Activation of JNK and p38 MAPK mediated by ZDHHC17 drives glioblastoma multiforme development and malignant progression. Theranostics. 2020;10(3):998–1015. doi: 10.7150/thno.40076
  21. Lin SP, Lee YT, Wang JY, et al. Survival of cancer stem cells under hypoxia and serum depletion via decrease in PP2A activity and activation of p38-MAPKAPK2-Hsp27. PLoS One. 2012;7(11):e49605. doi: 10.1371/journal.pone.0049605
  22. Ouédraogo ZG, Biau J, Kemeny J-L, et al. Role of STAT3 in genesis and progression of human malignant gliomas. Mol Neurobiol. 2017;54(8):5780–5797. doi: 10.1007/s12035-016-0103-0
  23. Aroui S, Dardevet L, Najlaoui F, et al. PTEN-regulated AKT/FoxO3a/Bim signaling contributes to human cell glioblastoma apoptosis by platinum-maurocalcin conjugate. Int J Biochem Cell Biol. 2016;77(Pt A):15–22. doi: 10.1016/j.biocel.2016.05.013
  24. Medarova Z, Pantazopoulos P, Yoo B. Screening of potential miRNA therapeutics for the prevention of multi-drug resistance in cancer cells. Sci Rep. 2020;10(1):1970. doi: 10.1038/s41598-020-58919-2
  25. Zhang HD, Jiang LH, Sun DW, et al. The role of miR-130a in cancer. Breast Cancer. 2017;24(4):521–527. doi: 10.1007/s12282-017-0776-x
  26. Sui H, Cai GX, Pan SF, et al. miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. Mol Cancer Ther. 2014;13(12):3137–3151. doi: 10.1158/1535-7163.MCT-14-0167
  27. Li Z, Zhang J, Zheng H, et al. Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib, overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme. J Exp Clin Cancer Res. 2019;38(1):380. doi: 10.1186/s13046-019-1371-0
  28. Tursynbay Y, Zhang J, Li Z, et al. Pim-1 kinase as cancer drug target: An update. Biomed Rep. 2016;4(2):140–146. doi: 10.3892/br.2015.561
  29. Katayama K, Noguchi K, Sugimoto Y. Regulations of P-Glycoprotein/ABCB1/MDR1 in human cancer cells. N J Sci. 2014(2):1–10. doi: 10.1155/2014/476974
  30. Oberstadt MC, Bien-Möller S, Weitmann K, et al. Epigenetic modulation of the drug resistance genes MGMT, ABCB1 and ABCG2 in glioblastoma multiforme. BMC Cancer. 2013;13:617. doi: 10.1186/1471-2407-13-617
  31. Liu B, Guo Z, Dong H, et al. LRIG1, human EGFR inhibitor, reverses multidrug resistance through modulation of ABCB1 and ABCG2. Brain Res. 2015;1611:93–100. doi: 10.1016/j.brainres.2015.03.023
  32. Xi G, Best B, Mania-Farnell B, et al. therapeutic potential for bone morphogenetic protein 4 in human malignant glioma. Neoplasia. 2017;19(4):261–270. doi: 10.1016/j.neo.2017.01.006
  33. Zhang X, Ding K, Wang J, et al. Chemoresistance caused by the microenvironment of glioblastoma and the corresponding solutions. Biomed Pharmacother. 2019;109:39–46. doi: 10.1016/j.biopha.2018.10.063
  34. Said HM, Hagemann C, Carta F, et al. Hypoxia induced CA9 inhibitory targeting by two different sulfonamide derivatives including acetazolamide in human glioblastoma. Bioorg Med Chem. 2013;21(13):3949–3957. doi: 10.1016/j.bmc.2013.03.068
  35. Pölönen P, Jawahar Deen A, Leinonen HM, et al. Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma. Oncogene. 2019;38(50):7473–7490. doi: 10.1038/s41388-019-0956-6
  36. Zhang L, Yang H, Zhang W, et al. Clk1-regulated aerobic glycolysis is involved in gliomas chemoresistance. J Neurochem. 2017;142(4):574–588. doi: 10.1111/jnc.14096
  37. Tivnan A, Zakaria Z, O’Leary C, et al. Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme. Front Neurosci. 2015;9:218. doi: 10.3389/fnins.2015.00218
  38. Begicevic R-R, Falasca M. ABC transporters in cancer stem cells: beyond chemoresistance. Int J Mol Sci. 2017;18(11):2362. doi: 10.3390/ijms18112362
  39. Johnson ZL, Chen J. Structural basis of substrate recognition by the multidrug resistance protein MRP1. Cell. 2017;168(6):1075–1085.e9. doi: 10.1016/j.cell.2017.01.041
  40. Zhang YK, Wang YJ, Gupta P, Chen ZS. Multidrug resistance proteins (MRPs) and cancer therapy. AAPS J. 2015;17(4):802–812. doi: 10.1208/s12248-015-9757-1
  41. Pattabiraman PP, Pecen PE, Rao PV. MRP4-mediated regulation of intracellular cAMP and cGMP levels in trabecular meshwork cells and homeostasis of intraocular pressure. Invest Ophthalmol Vis Sci. 2013;54(3):1636–1649. doi: 10.1167/iovs.12-11107
  42. Mao X, He Z, Zhou F, et al. Prognostic significance and molecular mechanisms of adenosine triphosphate-binding cassette subfamily C members in gastric cancer. Medicine (Baltimore). 2019;98(50):e18347. doi: 10.1097/MD.0000000000018347
  43. Bhuvanalakshmi G, Arfuso F, Millward M, et al. Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties. PLoS One. 2015;10(6):e0127517. doi: 10.1371/journal.pone.0127517
  44. Kosalai ST, Abdelrazak Morsy MH, Papakonstantinou N, et al. EZH2 upregulates the PI3K/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia. Epigenetics. 2019;14(11):1125–1140. doi: 10.1080/15592294.2019.1633867
  45. Navarro L, Gil-Benso R, Megías J, et al. Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status. Neuroscience. 2015;297:243–251. doi: 10.1016/j.neuroscience.2015.04.005
  46. Guo G, Narayan RN, Horton L, et al. The Role of EGFR-Met interactions in the pathogenesis of glioblastoma and resistance to treatment. Curr Cancer Drug Targets. 2017;17(3):297–302. doi: 10.2174/1568009616666161215162515
  47. Kudinov AE, Karanicolas J, Golemis EA, Boumber Y. Musashi RNA-Binding proteins as cancer drivers and novel therapeutic targets. Clin Cancer Res. 2017;23(9):2143–2153. doi: 10.1158/1078-0432.CCR-16-2728
  48. Shahi MH, Farheen S, Mariyath MP, Castresana JS. Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance. Tumour Biol. 2016;37(11):15107–15114. doi: 10.1007/s13277-016-5365-7
  49. Rama AR, Alvarez PJ, Madeddu R, Aranega A. ABC transporters as differentiation markers in glioblastoma cells. Mol Biol Rep. 2014;41(8):4847–4851. doi: 10.1007/s11033-014-3423-z
  50. Uribe D, Torres Á, Rocha JD, et al. Multidrug resistance in glioblastoma stem-like cells: Role of the hypoxic microenvironment and adenosine signaling. Mol Aspects Med. 2017;55:140–151. doi: 10.1016/j.mam.2017.01.009
  51. Navarro-Quiles C, Mateo-Bonmatí E, Micol JL. ABCE proteins: from molecules to development. Front Plant Sci. 2018;9:1125. doi: 10.3389/fpls.2018.01125
  52. Chen L, Shi L, Wang W, Zhou Y. ABCG2 downregulation in glioma stem cells enhances the therapeutic efficacy of demethoxycurcumin. Oncotarget. 2017;8(26):43237–43247. doi: 10.18632/oncotarget.18018
  53. Nakanishi T, Ross D. Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression. Chin J Cancer. 2012;31(2):73–99. doi: 10.5732/cjc.011.10320
  54. Goncalves J, Bicker J, Alves G, et al. Relevance of breast cancer resistance protein to brain distribution and central acting drugs: A pharmacokinetic perspective. Curr Drug Metab. 2018;19(12):1021–1041. doi: 10.2174/1389200219666180629121033
  55. Shi L, Wang Z, Sun G, et al. miR-145 inhibits migration and invasion of glioma stem cells by targeting ABCG2. Neuromolecular Med. 2014;16(2):517–528. doi: 10.1007/s12017-014-8305-y
  56. Tian S, Yong M, Zhu J, et al. Enhancement of the effect of Methyl Pyropheophorbide-a-Mediated photodynamic therapy was achieved by increasing ROS through inhibition of Nrf2-HO-1 or Nrf2-ABCG2 signaling. Anticancer Agents Med Chem. 2017;17(13):1824–1836. doi: 10.2174/1871520617666170327145857
  57. Agarwal S, Hartz AMS, Elmquist WF, Bauer B. Breast cancer resistance protein and P-glycoprotein in brain cancer: Two gatekeepers team up. Curr Pharm Des. 2011;17(26):2793–2802. doi: 10.2174/138161211797440186
  58. Martin V, Xu J, Pabbisetty SK, et al. Tie2-mediated multidrug resistance in malignant gliomas is associated with upregulation of ABC transporters. Oncogene. 2009;28(24):2358–2363. doi: 10.1038/onc.2009.103
  59. Jin Y, Bin ZQ, Qiang H, et al. ABCG2 is related with the grade of glioma and resistance to mitoxantone, a chemotherapeutic drug for glioma. J Cancer Res Clin Oncol. 2009;135(10):1369–1376. doi: 10.1007/s00432-009-0578-4
  60. Wijaya J, Fukuda Y, Schuetz JD. Obstacles to brain tumor therapy: Key ABC transporters. Int J Mol Sci. 2017;18(12):2544. doi: 10.3390/ijms18122544
  61. Reardon DA, Conrad CA, Cloughesy T, et al. Phase I study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients. Cancer Chemother Pharmacol. 2012;69(6):1507–1518. doi: 10.1007/s00280-012-1854-6
  62. Nayak L, de Groot J, Wefel JS, et al. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas. J Neurooncol. 2017;132(1):181–188. doi: 10.1007/s11060-016-2357-9
  63. Herrlinger U, Schäfer N, Steinbach JP, et al. bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-Methylguanine-DNA methyltransferase nonmethylated glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol. 2016;34(14):1611–1619. doi: 10.1200/JCO.2015.63.4691
  64. Lu-Emerson C, Duda DG, Emblem KE, et al. Lessons from anti-vascular endothelial growth factor and anti-vascular endothelial growth factor receptor trials in patients with glioblastoma. J Clin Oncol. 2015;33(10):1197–1213. doi: 10.1200/JCO.2014.55.9575
  65. Chheda MG, Wen PY, Hochberg FH, et al. Vandetanib plus sirolimus in adults with recurrent glioblastoma: results of a phase I and dose expansion cohort study. J Neurooncol. 2015;121(3):627–634. doi: 10.1007/s11060-014-1680-2
  66. Pearson J, Regad T. Targeting cellular pathways in glioblastoma multiforme. Sig Transduct Target Ther. 2017;2:17040. doi: 10.1038/sigtrans.2017.40
  67. Arif SH, Pandith AA, Tabasum R, et al. Significant effect of anti-tyrosine kinase inhibitor (gefitinib) on overall survival of the glioblastoma multiforme patients in the backdrop of mutational status of epidermal growth factor receptor and PTEN genes. Asian J Neurosurg. 2018;13(1):46–52. doi: 10.4103/ajns.AJNS_95_17
  68. Molife LR, Dean EJ, Blanco-Codesido M, et al. A phase I, dose-escalation study of the multitargeted receptor tyrosine kinase inhibitor, golvatinib, in patients with advanced solid tumors. Clin Cancer Res. 2014;20(24):6284–6294. doi: 10.1158/1078-0432.CCR-14-0409
  69. Padovan M, Eoli M, Pellerino A, et al. Depatuxizumab mafodotin (Depatux-M) plus temozolomide in recurrent glioblastoma patients: Real-world experience from a multicenter study of Italian Association of Neuro-Oncology (AINO). Cancers (Basel). 2021;13(11):2773. doi: 10.3390/cancers13112773
  70. Wen PY, Drappatz J, de Groot J, et al. Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy. Neuro Oncol. 2018;20(2):249–258. doi: 10.1093/neuonc/nox154
  71. Yu A, Faiq N, Green S, et al. Report of safety of pulse dosing of lapatinib with temozolomide and radiation therapy for newly-diagnosed glioblastoma in a pilot phase II study. J Neurooncol. 2017;134(2):357–362. doi: 10.1007/s11060-017-2533-6
  72. Li J, Zou C-L, Zhang Z-M, et al. A multi-targeted tyrosine kinase inhibitor lenvatinib for the treatment of mice with advanced glioblastoma. Mol Med Rep. 2017;16(5):7105–7111. doi: 10.3892/mmr.2017.7456
  73. Westphal M, Heese O, Steinbach JP, et al. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer. 2015;51(4):522–532. doi: 10.1016/j.ejca.2014.12.019
  74. Olaratumab Completed Phase 2 Trials for Glioblastoma Multiforme, Adult Treatment. NCT00895180. https://go.drugbank.com/drugs/DB06043/clinical_trials?conditions=DBCOND0088047&phase=2&purpose=treatment&status=completed&__cf_chl_jschl_tk__=pmd_cEbWshGFMGoqes6n_B7D0tXCsfTuqIh_en6wF52PFuw-1629969594-0-gqNtZGzNApCjcnBszQiR
  75. Morley R, Cardenas A, Hawkins P, et al. Safety of onartuzumab in patients with solid tumors: Experience to date from the Onartuzumab Clinical Trial Program. PLoS One. 2015;10(10):e0139679. doi: 10.1371/journal.pone.0139679
  76. Cloughesy T, Finocchiaro G, Belda-Iniesta C, et al. Randomized, double-blind, placebo-controlled, multicenter phase II study of onartuzumab plus bevacizumab versus placebo plus bevacizumab in patients with recurrent glioblastoma: efficacy, safety, and hepatocyte growth factor and O6-Methylguanine-DNA methyltransferase biomarker analyses. J Clin Oncol. 2017;35(3):343–351. doi: 10.1200/JCO.2015.64.7685
  77. Pazopanib Completed Phase 2 Trials for Glioblastoma Multiforme (GBM) / Central Nervous System Neoplasms / Neoplasms, Brain / Gliosarcoma Treatment. NCT01931098 [Internet]. Available from: https://go.drugbank.com/drugs/DB06589/clinical_trials?conditions=DBCOND0032525%2CDBCOND0046976%2CDBCOND0002894%2CDBCOND0054211&phase=2&purpose=treatment&status=completed. Accessed: Dec 18, 2021.
  78. Panitumumab and Irinotecan for Malignant Gliomas [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT01017653. Accessed: Dec 18, 2021.
  79. Dean L, Kane M, Pratt VM, et al. Pertuzumab Therapy and ERBB2 Genotype. In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012–2015.
  80. Adult Glioblastoma Multiforme Completed Phase 2 Trials for Ramucirumab (DB05578). NCT00895180 [Internet]. Available from: https://go.drugbank.com/indications/DBCOND0088047/clinical_trials/DB05578?phase=2&status=completed. Accessed: Dec 18, 2021.
  81. Affronti ML, Jackman JG, McSherry F, et al. Phase II study to evaluate the efficacy and safety of rilotumumab and bevacizumab in subjects with recurrent malignant glioma. Oncologist. 2018;23(8):889–e98. doi: 10.1634/theoncologist.2018-0149
  82. Weller M, Butowski N, Tran DD, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):1373–1385. doi: 10.1016/S1470-2045(17)30517-X
  83. Nghiemphu PL, Ebiana VA, Wen P, et al. Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02. J Neurooncol. 2018;136(1):79–86. doi: 10.1007/s11060-017-2624-4
  84. Grisanti S, Ferrari VD, Buglione M, et al. Second line treatment of recurrent glioblastoma with sunitinib: results of a phase II study and systematic review of literature. J Neurosurg Sci. 2019;63(4):458–467. doi: 10.23736/S0390-5616.16.03874-1
  85. Torres Á, Arriagada V, Erices JI, et al. FK506 Attenuates the MRP1-mediated chemoresistant phenotype in glioblastoma stem-like cells. Int J Mol Sci. 2018;19(9):2697. doi: 10.3390/ijms19092697
  86. Schiff D, Jaeckle KA, Anderson SK, et al. Phase I/II trial of temsirolimus and sorafenib in treatment of patients with recurrent glioblastoma: North Central Cancer Treatment Group Study/Alliance N0572. Cancer. 2018;124(7):1455–1463. doi: 10.1002/cncr.31219
  87. Wu Y, Li Z, Zhang L, Liu G. Tivantinib hampers the proliferation of glioblastoma cells via PI3K/Akt/Mammalian target of rapamycin (mTOR) signaling. Med Sci Monit. 2019;25:7383–7390. doi: 10.12659/MSM.919319
  88. Kalpathy-Cramer J, Chandra V, Da X, et al. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. J Neurooncol. 2017;131(3):603–610. doi: 10.1007/s11060-016-2332-5
  89. Askoxylakis V, Ferraro GB, Kodack DP, et al. Preclinical efficacy of Ado-trastuzumab Emtansine in the brain microenvironment. J Natl Cancer Inst. 2015;108(2):djv313. doi: 10.1093/jnci/djv313
  90. Bauman JE, Ohr J, Gooding WE, et al. Phase I study of ficlatuzumab and cetuximab in cetuximab-resistant, recurrent/metastatic head and neck cancer. Cancers (Basel). 2020;12(6):1537. doi: 10.3390/cancers12061537
  91. Brown N, McBain C, Nash S, et al. Multi-center randomized phase II study comparing cediranib plus gefitinib with cediranib plus placebo in subjects with recurrent/progressive glioblastoma. PLoS One. 2016;11(5):e0156369. doi: 10.1371/journal.pone.0156369
  92. Super-Selective Intraarterial Cerebral Infusion of Cetuximab (Erbitux) for Treatment of Relapsed/Refractory GBM and AA. NCT01238237 [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT01238237. Accessed: Dec 18, 2021.
  93. Stupp R, Hegi ME, Gorlia T, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1100–1108. doi: 10.1016/S1470-2045(14)70379-1
  94. Miklja Z, Yadav VN, Cartaxo RT, et al. Everolimus improves the efficacy of dasatinib in PDGFRα-driven glioma. J Clin Invest. 2020;130(10):5313–5325. doi: 10.1172/JCI133310
  95. Chinnaiyan P, Won M, Wen PY, et al. A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG Oncology RTOG 0913. Neuro Oncol. 2018;20(5):666–673. doi: 10.1093/neuonc/nox209
  96. Tucker N. Enzastaurin Dosed in first phase 3 Study of newly diagnosed glioblastoma multiforme [Internet]. Available from: https://www.targetedonc.com/view/enzastaurin-dosed-in-first-phase-3-study-of-newly-diagnosed-glioblastoma-multiforme. Accessed: Dec 18, 2021.
  97. Erlotinib in treating patients with recurrent or progressive glioblastoma multiforme. NCT00054496 [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT00054496. Accessed: Dec 18, 2021.
  98. Brown CE, Badie B, Barish ME, et al. Bioactivity and safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in patients with recurrent glioblastoma. Clin Cancer Res. 2015;21(18):4062–4072. doi: 10.1158/1078-0432.CCR-15-0428
  99. Li L, Quang TS, Gracely EJ, et al. A Phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme. J Neurosurg. 2010;113(2):192–198. doi: 10.3171/2010.2.JNS091211
  100. Van den Bent M, Azaro A, De Vos F, et al. A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma. J Neurooncol. 2020;146(1):79–89. doi: 10.1007/s11060-019-03337-2
  101. Cleary JM, Reardon DA, Azad N, et al. A phase 1 study of ABT-806 in subjects with advanced solid tumors. Invest New Drugs. 2015;33(3):671–678. doi: 10.1007/s10637-015-0234-6
  102. Hoffman LM, Fouladi M, Olson J, et al. Phase I trial of weekly MK-0752 in children with refractory central nervous system malignancies: A Pediatric Brain Tumor Consortium Study. Childs Nerv Syst. 2015;31(8):1283–1289. doi: 10.1007/s00381-015-2725-3
  103. Lassen U, Chinot OL, McBain C, et al. Phase 1 dose-escalation study of the antiplacental growth factor monoclonal antibody RO5323441 combined with bevacizumab in patients with recurrent glioblastoma. Neuro Oncol. 2015;17(7):1007–1015. doi: 10.1093/neuonc/nov019
  104. Tortorella S, Karagiannis TC. Transferrin receptor-mediated endocytosis: a useful target for cancer therapy. J Membr Biol. 2014;247(4):291–307. doi: 10.1007/s00232-014-9637-0
  105. Yaylim I, Azam S, Farooqi AA, et al. Critical molecular and genetic markers in primary brain tumors with their clinical importance. In: Neurooncology – Newer Developments. Chapter 6. IntechOpen; 2016. doi: 10.5772/63550
  106. Zhao H, Chen G, Liang H, Dual PI3K/mTOR Inhibitor, XL765, suppresses glioblastoma growth by inducing ER stress-dependent apoptosis. Onco Targets Ther. 2019;12:5415–5424. doi: 10.2147/OTT.S210128
  107. Shukla S, Robey RW, Bates SE, Ambudkar SV. Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos. 2009;37(2):359–365. doi: 10.1124/dmd.108.024612
  108. Englund G, Lundquist P, Skogastierna C, et al. Cytochrome p450 inhibitory properties of common efflux transporter inhibitors. Drug Metab Dispos. 2014;42(3):441–447. doi: 10.1124/dmd.113.054932
  109. Declèves X, Bihorel S, Debray M, et al. ABC transporters and the accumulation of imatinib and its active metabolite CGP74588 in rat C6 glioma cells. Pharmacol Res. 2008;57(3):214–222. doi: 10.1016/j.phrs.2008.01.006
  110. Eadie LN, Hughes TP, White DL. Interaction of the efflux transporters ABCB1 and ABCG2 with imatinib, nilotinib, and dasatinib. Clin Pharmacol Ther. 2014;95(3):294–306. doi: 10.1038/clpt.2013.208
  111. Pun NT, Jeong C-H. Statin as a potential chemotherapeutic agent: current updates as a monotherapy, combination therapy, and treatment for anti-cancer drug resistance. Pharmaceuticals (Basel). 2021;14(5):470. doi: 10.3390/ph14050470
  112. Nguyen TT, Duong VA, Maeng HJ. Pharmaceutical formulations with P-Glycoprotein inhibitory effect as promising approaches for enhancing oral drug absorption and bioavailability. Pharmaceutics. 2021;13(7):1103. doi: 10.3390/pharmaceutics13071103
  113. Toyoda Y, Takada T, Suzuki H. Inhibitors of human ABCG2: from technical background to recent updates with clinical implications. Front Pharmacol. 2019;10:208. doi: 10.3389/fphar.2019.00208
  114. Martín V, Sanchez-Sanchez AM, Herrera F, et al. Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells. Br J Cancer. 2013;108(10):2005–2012. doi: 10.1038/bjc.2013.188
  115. You D, Richardson JR, Aleksunes LM. Epigenetic regulation of multidrug resistance protein 1 and breast cancer resistance protein transporters by histone deacetylase inhibition. Drug Metab Dispos. 2020;48(6):459–480. doi: 10.1124/dmd.119.089953
  116. Lv S, Teugels E, Sadones J, et al. Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab. Int J Oncol. 2012;41(3):1029–1035. doi: 10.3892/ijo.2012.1539
  117. Lamballe F, Toscano S, Conti F, et al. Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells. Oncotarget. 2016;7(46):74747–74767. doi: 10.18632/oncotarget.12546
  118. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699–708. doi: 10.1056/NEJMoa1308573
  119. Radoul M, Chaumeil MM, Eriksson P, et al. MR studies of glioblastoma models treated with dual PI3K/mTOR inhibitor and temozolomide: metabolic changes are associated with enhanced survival. Mol Cancer Ther. 2016;15(5):1113–1122. doi: 10.1158/1535-7163.MCT-15-0769
  120. Garrido W, Muñoz M, San Martín R, Quezada C. FK506 confers chemosensitivity to anticancer drugs in glioblastoma multiforme cells by decreasing the expression of the multiple resistance-associated protein-1. Biochem Biophys Res Commun. 2011;411(1):62–68. doi: 10.1016/j.bbrc.2011.06.087
  121. Lo H-W, Cao X, Zhu H, Ali-Osman F. Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to iressa and alkylators. Clin Cancer Res. 2008;14(19):6042–6054. doi: 10.1158/1078-0432.CCR-07-4923
  122. Miyata H, Ashizawa T, Iizuka A, et al. Combination of a STAT3 inhibitor and an mTOR inhibitor against a temozolomide-resistant glioblastoma cell line. Cancer Genomics Proteomics. 2017;14(1):83–91. doi: 10.21873/cgp.20021
  123. Zanotto-Filho A, Braganhol E, Schröder R, et al. NF-κB inhibitors induce cell death in glioblastomas. Biochem Pharmacol. 2011;81(3):412–424. doi: 10.1016/j.bcp.2010.10.014
  124. Castro-Gamero AM, Borges KS, Moreno DA, et al. Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells. Invest New Drugs. 2013;31(4):858–870. doi: 10.1007/s10637-012-9917-4
  125. Chen R, Zhang M, Zhou Y, et al. The application of histone deacetylases inhibitors in glioblastoma. J Exp Clin Cancer Res. 2020;39(1):138. doi: 10.1186/s13046-020-01643-6
  126. Ko CY, Lin CH, Chuang JY, et al. MDM2 degrades deacetylated nucleolin through ubiquitination to promote glioma stem-like cell enrichment for chemotherapeutic resistance. Mol Neurobiol. 2018;55(4):3211–3223. doi: 10.1007/s12035-017-0569-4
  127. Hsu CC, Chang WC, Hsu TI, et al. Suberoylanilide hydroxamic acid represses glioma stem-like cells. J Biomed Sci. 2016;23(1):81. doi: 10.1186/s12929-016-0296-6
  128. Wu Y, Dong L, Bao S, et al. FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways. Biomed Pharmacother. 2016;84:462–469. doi: 10.1016/j.biopha.2016.09.051
  129. Li ZY, Li QZ, Chen L, et al. Histone deacetylase inhibitor RGFP109 overcomes temozolomide resistance by blocking NF-κB-dependent transcription in glioblastoma cell lines. Neurochem Res. 2016;41(12):3192–3205. doi: 10.1007/s11064-016-2043-5
  130. Banelli B, Daga A, Forlani A, et al. Small molecules targeting histone demethylase genes (KDMs) inhibit growth of temozolomide-resistant glioblastoma cells. Oncotarget. 2017;8(21):34896–34910. doi: 10.18632/oncotarget.16820
  131. Romani M, Daga A, Forlani A, et al. Targeting of histone demethylases KDM5A and KDM6B inhibits the proliferation of temozolomide-resistant glioblastoma cells. Cancers (basel). 2019;11(6):878. doi: 10.3390/cancers11060878
  132. Nie E, Jin X, Wu W, et al. MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT. J Neurooncol. 2017;133(1):59–68. doi: 10.1007/s11060-017-2425-9
  133. Riganti C, Salaroglio IC, Pinzòn-Daza ML, et al. Temozolomide down-regulates P-glycoprotein in human blood-brain barrier cells by disrupting Wnt3 signaling. Cell Mol Life Sci. 2014;71(3):499–516. doi: 10.1007/s00018-013-1397-y
  134. Jakubowicz-Gil J, Bądziul D, Langner E, et al. Temozolomide and sorafenib as programmed cell death inducers of human glioma cells. Pharmacol Rep. 2017;69(4):779–787. doi: 10.1016/j.pharep.2017.03.008
  135. Stavrovskaya AA, Shushanov SS, Rybalkina EY. Problems of glioblastoma multiforme drug resistance. Biochemistry (Mosc). 2016;81(2):91–100. doi: 10.1134/S0006297916020036
  136. Yu F, Li G, Gao J, et al. SPOCK1 is upregulated in recurrent glioblastoma and contributes to metastasis and temozolomide resistance. Cell Prolif. 2016;49(2):195–206. doi: 10.1111/cpr.12241
  137. Garros-Regulez L, Aldaz P, Arrizabalaga O, et al. mTOR inhibition decreases SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance. Expert Opin Ther Targets. 2016;20(4):393–405. doi: 10.1517/14728222.2016.1151002
  138. Siebzehnrubl FA, Silver DJ, Tugertimur B, et al. The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance. EMBO Mol Med. 2013;5(8):1196–1212. doi: 10.1002/emmm.201302827
  139. Ciechomska IA, Przanowski P, Jackl J, et al. BIX01294, an inhibitor of histone methyltransferase, induces autophagy-dependent differentiation of glioma stem-like cells. Sci Rep. 2016;6:38723. doi: 10.1038/srep38723
  140. Jin F, Zhao L, Guo Y-J, et al. Influence of Etoposide on anti-apoptotic and multidrug resistance-associated protein genes in CD133 positive U251 glioblastoma stem-like cells. Brain Res. 2010;1336:103–111. doi: 10.1016/j.brainres.2010.04.005
  141. Bieler A, Mantwill K, Dravits T, et al. Novel three-pronged strategy to enhance cancer cell killing in glioblastoma cell lines: histone deacetylase inhibitor, chemotherapy, and oncolytic adenovirus dl520. Hum Gene Ther. 2006;17(1):55–70. doi: 10.1089/hum.2006.17.55
  142. Liu G, Akasaki Y, Khong HT, et al. Cytotoxic T cell targeting of TRP-2 sensitizes human malignant glioma to chemotherapy. Oncogene. 2005;24(33):5226–5234. doi: 10.1038/sj.onc.1208519
  143. Zheng LT, Lee S, Yin GN, et al. Down-regulation of lipocalin 2 contributes to chemoresistance in glioblastoma cells. J Neurochem. 2009;111(5):1238–1251. doi: 10.1111/j.1471-4159.2009.06410.x
  144. Kim BS, Kang KS, Choi JI, et al. Knockdown of the potential cancer stem-like cell marker Rex-1 improves chemotherapeutic effects in gliomas. Hum Gene Ther. 2011;22(12):1551–1562. doi: 10.1089/hum.2011.096
  145. Chou CW, Wang CC, Wu CP, et al. Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1. Neuro Oncol. 2012;14(10):1227–1238. doi: 10.1093/neuonc/nos195
  146. Pinzón-Daza M, Garzón R, Couraud P, et al. The association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cells. Br J Pharmacol. 2012;167(7):1431–1447. doi: 10.1111/j.1476-5381.2012.02103.x
  147. Valera ET, de Freitas Cortez MA, de Paula Queiroz RG, et al. Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine. Childs Nerv Syst. 2009;25(1):39–45. doi: 10.1007/s00381-008-0740-3
  148. Lun X, Wells JC, Grinshtein N, et al. Disulfiram when combined with copper enhances the therapeutic effects of temozolomide for the treatment of glioblastoma. Clin Cancer Res. 2016;22(15):3860–3875. doi: 10.1158/1078-0432.CCR-15-1798

Supplementary files

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1. Figure. Intracellular mechanisms of multidrug resistance of glioblastoma involving genes ABCB1 and ABCG2. See text for explanations

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