Abstract
Glioblastoma, the most common primary brain tumor, has been recognized as one of the most lethal and fatal human tumors. It has a dismal prognosis, and survival after diagnosis is less than 15 months. Surgery and radiotherapy are the only available treatment options at present. However, numerous approaches have been made to upgrade in vivo and in vitro models with the primary goal of assessing abnormal molecular pathways that would be suitable targets for novel therapeutic approaches. Novel drugs, delivery systems, and immunotherapy strategies to establish new multimodal therapies that target the molecular pathways involved in tumor initiation and progression in glioblastoma are being studied. The goal of this review was to describe the pathophysiology, neurodegeneration mechanisms, signaling pathways, and future therapeutic targets associated with glioblastomas. The key features have been detailed to provide an up-to-date summary of the advancement required in current diagnosis and therapeutics for glioblastoma. The role of nanoparticulate system graphene quantum dots as suitable therapy for glioblastoma has also been discussed.
Keywords: Glioblastoma, immunology, therapeutics, GQDs, cancer, diagnosis.
Graphical Abstract
[http://dx.doi.org/10.1186/1756-9966-30-87] [PMID: 21943236]
[http://dx.doi.org/10.1002/9780470988121]
[http://dx.doi.org/10.1093/carcin/21.3.485] [PMID: 10688869]
[http://dx.doi.org/10.3390/ijms16022942] [PMID: 25636036]
[http://dx.doi.org/10.1371/journal.pone.0037782] [PMID: 22719850]
[http://dx.doi.org/10.18632/aging.100934] [PMID: 27019364]
[http://dx.doi.org/10.1007/s13311-017-0519-x] [PMID: 28281173]
[http://dx.doi.org/10.1093/neuonc/nov269] [PMID: 26527735]
[http://dx.doi.org/10.3390/cancers3033242] [PMID: 24212955]
[http://dx.doi.org/10.2174/138920207782446160] [PMID: 19384426]
[http://dx.doi.org/10.1186/s12943-018-0792-2] [PMID: 29455659]
[http://dx.doi.org/10.1002/jcb.24976] [PMID: 25211508]
[http://dx.doi.org/10.1016/j.ebiom.2015.08.026] [PMID: 26629530]
[http://dx.doi.org/10.1038/aps.2016.167] [PMID: 28317871]
[http://dx.doi.org/10.2174/09298673113209990226] [PMID: 23992330]
[http://dx.doi.org/10.1136/gut.2006.106849] [PMID: 17339242]
[http://dx.doi.org/10.1093/nar/gkn341] [PMID: 18522974]
[http://dx.doi.org/10.1093/neuonc/nos135] [PMID: 22679124]
[http://dx.doi.org/10.1016/j.jocn.2014.10.013] [PMID: 25698543]
[PMID: 28239999]
[http://dx.doi.org/10.1634/theoncologist.2013-0345] [PMID: 24664484]
[PMID: 16551981]
[http://dx.doi.org/10.1146/annurev-pathol-121808-102109] [PMID: 19737106]
[PMID: 24711712]
[PMID: 20108752]
[PMID: 27144829]
[http://dx.doi.org/10.1007/978-1-60327-553-8_26]
[http://dx.doi.org/10.1016/j.nurt.2009.05.001] [PMID: 19560733]
[http://dx.doi.org/10.1038/nrc3298] [PMID: 22695393]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.3389/fonc.2019.00380] [PMID: 31157165]
[PMID: 24634853]
[http://dx.doi.org/10.7150/jca.17648] [PMID: 28382138]
[http://dx.doi.org/10.1016/j.apsb.2014.03.001] [PMID: 26579383]
[http://dx.doi.org/10.2147/vhrm.2006.2.3.213] [PMID: 17326328]
[http://dx.doi.org/10.1038/mtna.2016.90] [PMID: 27845769]
[http://dx.doi.org/10.1186/s13287-018-1060-5] [PMID: 30409213]
[http://dx.doi.org/10.1186/s13578-019-0327-6] [PMID: 31428311]
[http://dx.doi.org/10.20517/2394-4722.2015.72]
[http://dx.doi.org/10.2174/187152411794961095] [PMID: 20528763]
[http://dx.doi.org/10.18632/oncotarget.11575] [PMID: 27613841]
[http://dx.doi.org/10.1093/neuonc/nop011] [PMID: 20150373]
[http://dx.doi.org/10.1136/jnnp.2003.025031] [PMID: 15090567]
[PMID: 14522905]
[http://dx.doi.org/10.1080/19490976.2017.1356979] [PMID: 28816579]
[http://dx.doi.org/10.1002/ijc.28535] [PMID: 24127236]
[http://dx.doi.org/10.1016/j.cyto.2015.05.026] [PMID: 26088753]
[http://dx.doi.org/10.1080/19490976.2018.1441662] [PMID: 29543554]
[http://dx.doi.org/10.1038/ncpneuro0289] [PMID: 16932614]
[http://dx.doi.org/10.1080/19490976.2017.1361092] [PMID: 28786749]
[http://dx.doi.org/10.1177/0883073808321061] [PMID: 18952585]
[http://dx.doi.org/10.1016/j.ddmec.2013.03.004] [PMID: 24982684]
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2179] [PMID: 28254861]
[http://dx.doi.org/10.3892/etm.2011.367] [PMID: 22969836]
[http://dx.doi.org/10.1007/s11912-009-0077-4] [PMID: 20425605]
[http://dx.doi.org/10.3171/jns.2003.99.6.1018] [PMID: 14705730]
[http://dx.doi.org/10.1007/s10143-016-0709-8] [PMID: 27085859]
[PMID: 11290466]
[PMID: 10669230]
[http://dx.doi.org/10.1007/s13311-010-0002-4] [PMID: 21274681]
[http://dx.doi.org/10.3174/ajnr.A0872] [PMID: 18065516]
[http://dx.doi.org/10.1007/s00234-011-0947-y] [PMID: 21833736]
[http://dx.doi.org/10.3171/jns.2004.101.3.0476] [PMID: 15352606]
[http://dx.doi.org/10.1126/scitranslmed.aaa1009]
[http://dx.doi.org/10.1093/neuonc/nor054] [PMID: 21757446]
[http://dx.doi.org/10.1158/1535-7163.MCT-07-0047] [PMID: 17620423]
[http://dx.doi.org/10.1016/S0163-7258(03)00014-7] [PMID: 12667889]
[http://dx.doi.org/10.1016/j.nurt.2009.04.002] [PMID: 19560734]
[http://dx.doi.org/10.2174/1570164611310030007] [PMID: 24228024]
[http://dx.doi.org/10.3171/jns.2004.100.3.0431] [PMID: 15035278]
[http://dx.doi.org/10.1002/ijc.28455] [PMID: 24038033]
[http://dx.doi.org/10.1038/s41571-019-0177-5] [PMID: 30733593]
[http://dx.doi.org/10.1016/0360-3016(95)00123-G]
[http://dx.doi.org/10.1093/neuonc/not247] [PMID: 24470557]
[http://dx.doi.org/10.3109/02841869509127197] [PMID: 7576756]
[http://dx.doi.org/10.1093/jnci/87.1.34] [PMID: 7666461]
[http://dx.doi.org/10.1186/s40880-018-0299-7]
[http://dx.doi.org/10.1186/s13045-018-0683-4] [PMID: 30541578]
[http://dx.doi.org/10.1177/1078155210375858] [PMID: 20634263]
[http://dx.doi.org/10.1517/17425240903167942] [PMID: 19732031]
[http://dx.doi.org/10.1586/14737175.8.10.1457] [PMID: 18928341]
[http://dx.doi.org/10.1186/1471-2407-9-444] [PMID: 20015387]
[http://dx.doi.org/10.5732/cjc.011.10111] [PMID: 21718592]
[http://dx.doi.org/10.1215/S1152851705000050] [PMID: 16212809]
[http://dx.doi.org/10.1093/neuonc/nou222]
[http://dx.doi.org/10.3389/fonc.2018.00208] [PMID: 30018881]
[http://dx.doi.org/10.1016/0277-5379(88)90261-1] [PMID: 2833402]
[http://dx.doi.org/10.1039/C8DT00838H] [PMID: 29632935]
[http://dx.doi.org/10.1046/j.1365-2125.1999.00884.x] [PMID: 10190647]
[http://dx.doi.org/10.1093/annonc/mdi113] [PMID: 15728109]
[http://dx.doi.org/10.1093/jnci/djg017] [PMID: 12902441]
[http://dx.doi.org/10.1634/theoncologist.9-1-80] [PMID: 14755017]
[http://dx.doi.org/10.1016/S1096-2190(98)00033-X]
[http://dx.doi.org/10.1016/S1470-2045(00)00293-X] [PMID: 11905768]
[http://dx.doi.org/10.1177/1534735404270578] [PMID: 15523104]
[http://dx.doi.org/10.1002/(SICI)1097-0215(1998)78:11+<69:AID-IJC20>3.0.CO;2-7] [PMID: 9876483]
[http://dx.doi.org/10.1371/journal.pone.0152538] [PMID: 27031833]
[PMID: 30895270]
[http://dx.doi.org/10.1016/S2221-1691(15)30372-5]
[http://dx.doi.org/10.1016/j.ccr.2017.06.001]
[http://dx.doi.org/10.1016/j.mattod.2015.11.008]
[http://dx.doi.org/10.1021/am3030849] [PMID: 23339586]
[http://dx.doi.org/10.1039/C4NR07005D] [PMID: 25569453]
[http://dx.doi.org/10.1039/C6RA16516H]
[http://dx.doi.org/10.1038/s41565-018-0179-y] [PMID: 29988049]
[http://dx.doi.org/10.1016/j.msec.2018.09.020] [PMID: 30423706]
[http://dx.doi.org/10.1039/C6NR01697A] [PMID: 27094022]
[http://dx.doi.org/10.1016/j.colsurfb.2014.07.043] [PMID: 25129696]
[http://dx.doi.org/10.1039/C7RA11963A]
[http://dx.doi.org/10.1016/j.colsurfb.2010.07.035] [PMID: 20728319]
[http://dx.doi.org/10.1016/j.jcis.2011.01.052] [PMID: 21329939]
[http://dx.doi.org/10.1515/ntrev-2012-0078]
[http://dx.doi.org/10.1039/C6RA03759C]