conference banner
Abstract

Glioblastoma multiforme (GBM) is the most common type of cancer that affects the central nervous system (CNS). It currently accounts for about 2% of diagnosed malignant tumors worldwide, with 296,000 new cases reported per year. The first-choice treatment consists of surgical resection, radiotherapy, and adjuvant chemotherapy, which increases patients' survival by 15 months. New clinical and pre-clinical research aims to improve this prognosis by proposing the search for new drugs that effectively eliminate cancer cells, circumventing problems such as resistance to treatment. One of the promising therapeutic strategies in the treatment of GBM is the inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway, which is closely related to the process of tumor carcinogenesis. This review sought to address the main scientific studies of synthetic or natural drug prototypes that target specific therapy co-directed via the PI3K pathway, against human glioblastoma.

Keywords: Glioblastoma, therapy, phosphatidylinositol 3-kinase (PI3K), cancer, pharmacology, oncology.

Graphical Abstract
[1]
Kontomanolis, E.N.; Koutras, A.; Syllaios, A.; Schizas, D.; Mastoraki, A.; Garmpis, N.; Diakosavvas, M.; Angelou, K.; Tsatsaris, G.; Pagkalos, A.; Ntounis, T.; Fasoulakis, Z. Role of oncogenes and tumor-suppressor genes in carcinogenesis: A review. Anticancer Res., 2020, 40(11), 6009-6015.
[http://dx.doi.org/10.21873/anticanres.14622] [PMID: 33109539]
[2]
Anderson, N.M.; Simon, M.C. The tumor microenvironment. Curr. Biol., 2020, 30(16), R921-R925.
[http://dx.doi.org/10.1016/j.cub.2020.06.081] [PMID: 32810447]
[3]
Merabishvili, V. Cancer Incidence in Five Continents Volume XI; Bray, F.; Colombet, M.; Mery, L.; Piñeros, M.; Znaor, A.; Zanetti, R.; Ferlay, J., Eds.; IARC Scientific Publication, 2021. (166.)
[4]
Salimi, A.; Zali, A.; Seddighi, A.S.; Seddighi, A.; Meshkat, S.; Hosseini, M.; Nikouei, A.; Akbari, M.E. Descriptive epidemiology of brain and central nervous system tumours: Results from Iran national cancer registry, 2010-2014. J. Cancer Epidemiol., 2020, 2020, 1-10.
[http://dx.doi.org/10.1155/2020/3534641] [PMID: 33014059]
[5]
Stewart, B.W. World Health Organization, For A, De M, Cancer L. World cancer report; Iarc Press: Lyon, 2014.
[7]
Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.; Burger, P.C.; Jouvet, A.; Scheithauer, B.W.; Kleihues, P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol., 2007, 114(2), 97-109.
[http://dx.doi.org/10.1007/s00401-007-0243-4] [PMID: 17618441]
[8]
Thakkar, J.P.; Dolecek, T.A.; Horbinski, C.; Ostrom, Q.T.; Lightner, D.D.; Barnholtz-Sloan, J.S.; Villano, J.L. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol. Biomarkers Prev., 2014, 23(10), 1985-1996.
[http://dx.doi.org/10.1158/1055-9965.EPI-14-0275] [PMID: 25053711]
[9]
Tan, A.C.; Ashley, D.M.; López, G.Y.; Malinzak, M.; Friedman, H.S.; Khasraw, M. Management of glioblastoma: State of the art and future directions. CA Cancer J. Clin., 2020, 70(4), 299-312.
[http://dx.doi.org/10.3322/caac.21613] [PMID: 32478924]
[10]
Alexander, B.M.; Cloughesy, T.F. Adult Glioblastoma. J. Clin. Oncol., 2017, 35(21), 2402-2409.
[http://dx.doi.org/10.1200/JCO.2017.73.0119] [PMID: 28640706]
[11]
DeCordova, S.; Shastri, A.; Tsolaki, A.G.; Yasmin, H.; Klein, L.; Singh, S.K.; Kishore, U. Molecular heterogeneity and immunosuppressive microenvironment in glioblastoma. Front. Immunol., 2020, 11, 1402.
[http://dx.doi.org/10.3389/fimmu.2020.01402] [PMID: 32765498]
[12]
Ostrom, Q.T.; Gittleman, H.; Liao, P.; Vecchione-Koval, T.; Wolinsky, Y.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro-oncol., 2017, 19(S5), v1-v88.
[http://dx.doi.org/10.1093/neuonc/nox158] [PMID: 29117289]
[13]
Żukiel, R.; Piestrzeniewicz, R.; Nowak, S.; Jankowski, R.; Wieloch, M. Historia leczenia operacyjnego guzów mózgu. Neuroskop., 2004, 6, 9-19.
[14]
Louis, D.N.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol., 2016, 131(6), 803-820.
[http://dx.doi.org/10.1007/s00401-016-1545-1] [PMID: 27157931]
[15]
Wen, P.Y.; Packer, R.J. The 2021 WHO classification of tumors of the central nervous system: Clinical implications. Neuro-oncol., 2021, 23(8), 1215-1217.
[http://dx.doi.org/10.1093/neuonc/noab120] [PMID: 34185090]
[16]
Zhou, Y.S.; Wang, W.; Chen, N.; Wang, L.C.; Huang, J.B. Research progress of anti-glioma chemotherapeutic drugs (Review). Oncol. Rep., 2022, 47(5), 101.
[http://dx.doi.org/10.3892/or.2022.8312] [PMID: 35362540]
[17]
Louis, D.N.; Perry, A.; Wesseling, P.; Brat, D.J.; Cree, I.A.; Figarella-Branger, D.; Hawkins, C.; Ng, H.K.; Pfister, S.M.; Reifenberger, G.; Soffietti, R.; von Deimling, A.; Ellison, D.W. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro-oncol., 2021, 23(8), 1231-1251.
[http://dx.doi.org/10.1093/neuonc/noab106] [PMID: 34185076]
[18]
Cruz, J.V.R.; Batista, C.; Afonso, B.H.; Alexandre-Moreira, M.S.; Dubois, L.G.; Pontes, B.; Moura Neto, V.; Mendes, F.A. Obstacles to glioblastoma treatment two decades after temozolomide. Cancers., 2022, 14(13), 3203.
[http://dx.doi.org/10.3390/cancers14133203] [PMID: 35804976]
[19]
Olar, A.; Wani, K.M.; Alfaro-Munoz, K.D.; Heathcock, L.E.; van Thuijl, H.F.; Gilbert, M.R.; Armstrong, T.S.; Sulman, E.P.; Cahill, D.P.; Vera-Bolanos, E.; Yuan, Y.; Reijneveld, J.C.; Ylstra, B.; Wesseling, P.; Aldape, K.D. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas. Acta Neuropathol., 2015, 129(4), 585-596.
[http://dx.doi.org/10.1007/s00401-015-1398-z] [PMID: 25701198]
[20]
Ohgaki, H.; Kleihues, P. The definition of primary and secondary glioblastoma. Clin. Cancer Res., 2013, 19(4), 764-772.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3002] [PMID: 23209033]
[21]
Cancer biology: Molecular and genetic basis - Oncology for Medical Students. wiki.cancer.org.au
[22]
Nayak, A.; Ralte, A.M.; Sharma, M.C.; Singh, V.P.; Mahapatra, A.K.; Mehta, V.S.; Sarkar, C. p53 protein alterations in adult astrocytic tumors and oligodendrogliomas. Neurol. India, 2004, 52(2), 228-232.
[PMID: 15269478]
[23]
Hanif, F.; Muzaffar, K.; Perveen, K.; Malhi, S.M.; Simjee, ShU. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac. J. Cancer Prev., 2017, 18(1), 3-9.
[PMID: 28239999]
[24]
Birbilis, T.A.; Matis, G.K.; Eleftheriadis, S.G.; Theodoropoulou, E.N.; Sivridis, E. Spinal metastasis of glioblastoma multiforme: An uncommon suspect? Spine., 2010, 35(7), E264-E269.
[http://dx.doi.org/10.1097/BRS.0b013e3181c11748] [PMID: 20195200]
[25]
Lun, M.; Lok, E.; Gautam, S.; Wu, E.; Wong, E.T. The natural history of extracranial metastasis from glioblastoma multiforme. J. Neurooncol., 2011, 105(2), 261-273.
[http://dx.doi.org/10.1007/s11060-011-0575-8] [PMID: 21512826]
[26]
Urbańska, K.; Sokołowska, J.; Szmidt, M.; Sysa, P. Review Glioblastoma multiforme – an overview. Contemp. Oncol., 2014, 5(5), 307-312.
[http://dx.doi.org/10.5114/wo.2014.40559] [PMID: 25477751]
[27]
Lohmann, P.; Werner, J.M.; Shah, N.; Fink, G.; Langen, K.J.; Galldiks, N. Combined amino acid positron emission tomography and advanced magnetic resonance imaging in glioma patients. Cancers., 2019, 11(2), 153.
[http://dx.doi.org/10.3390/cancers11020153] [PMID: 30699942]
[28]
Liu, S.; Shi, W.; Zhao, Q.; Zheng, Z.; Liu, Z.; Meng, L.; Dong, L.; Jiang, X. Progress and prospect in tumor treating fields treatment of glioblastoma. Biomed. Pharmacother., 2021, 141, 111810.
[http://dx.doi.org/10.1016/j.biopha.2021.111810] [PMID: 34214730]
[29]
Katsetos, C.D.; Dráberová, E.; Legido, A.; Dumontet, C.; Dráber, P. Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. class III β-tubulin. J. Cell. Physiol., 2009, 221(3), 505-513.
[http://dx.doi.org/10.1002/jcp.21870] [PMID: 19650075]
[30]
Mehta, S.; Lo Cascio, C. Developmentally regulated signaling pathways in glioma invasion. Cell. Mol. Life Sci., 2018, 75(3), 385-402.
[http://dx.doi.org/10.1007/s00018-017-2608-8] [PMID: 28821904]
[31]
Haumann, R.; Videira, J.C.; Kaspers, G.J.L.; van Vuurden, D.G.; Hulleman, E. Overview of current drug delivery methods across the blood–brain barrier for the treatment of primary brain tumors. CNS Drugs., 2020, 34(11), 1121-1131.
[http://dx.doi.org/10.1007/s40263-020-00766-w] [PMID: 32965590]
[32]
Spangle, J.M.; Roberts, T.M.; Zhao, J.J. The emerging role of PI3K/AKT-mediated epigenetic regulation in cancer. Biochim. Biophys. Acta Rev. Cancer, 2017, 1868(1), 123-131.
[http://dx.doi.org/10.1016/j.bbcan.2017.03.002] [PMID: 28315368]
[33]
Kaplan, D.R.; Whitman, M.; Schaffhausen, B.; Pallas, D.C.; White, M.; Cantley, L.; Roberts, T.M. Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity. Cell, 1987, 50(7), 1021-1029.
[http://dx.doi.org/10.1016/0092-8674(87)90168-1] [PMID: 2441878]
[34]
Martini, M.; De Santis, M.C.; Braccini, L.; Gulluni, F.; Hirsch, E. PI3K/AKT signaling pathway and cancer: An updated review. Ann. Med., 2014, 46(6), 372-383.
[http://dx.doi.org/10.3109/07853890.2014.912836] [PMID: 24897931]
[35]
El Sheikh, S.S.; Domin, J.; Tomtitchong, P.; Abel, P.; Stamp, G.; Lalani, E.N. Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation. BMC Clin. Pathol., 2003, 3(1), 4.
[http://dx.doi.org/10.1186/1472-6890-3-4] [PMID: 14563213]
[36]
Vivanco, I.; Sawyers, C.L. The phosphatidylinositol 3-Kinase–AKT pathway in human cancer. Nat. Rev. Cancer, 2002, 2(7), 489-501.
[http://dx.doi.org/10.1038/nrc839] [PMID: 12094235]
[37]
Alzahrani, A.S. PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside. Semin. Cancer Biol., 2019, 59, 125-132.
[http://dx.doi.org/10.1016/j.semcancer.2019.07.009] [PMID: 31323288]
[38]
Hay, N.; Sonenberg, N. Upstream and downstream of mTOR. Genes Dev., 2004, 18(16), 1926-1945.
[http://dx.doi.org/10.1101/gad.1212704] [PMID: 15314020]
[39]
Murugan, A.K. mTOR: Role in cancer, metastasis and drug resistance. Semin. Cancer Biol., 2019, 59, 92-111.
[http://dx.doi.org/10.1016/j.semcancer.2019.07.003] [PMID: 31408724]
[40]
Liu, P.; Cheng, H.; Roberts, T.M.; Zhao, J.J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat. Rev. Drug Discov., 2009, 8(8), 627-644.
[http://dx.doi.org/10.1038/nrd2926] [PMID: 19644473]
[41]
Noorolyai, S.; Shajari, N.; Baghbani, E.; Sadreddini, S.; Baradaran, B. The relation between PI3K/AKT signalling pathway and cancer. Gene, 2019, 698, 120-128.
[http://dx.doi.org/10.1016/j.gene.2019.02.076] [PMID: 30849534]
[42]
Squarize, C.H.; Castilho, R.M.; Abrahao, A.C.; Molinolo, A.; Lingen, M.W.; Gutkind, J.S. PTEN deficiency contributes to the development and progression of head and neck cancer. Neoplasia., 2013, 15(5), 461-471.
[http://dx.doi.org/10.1593/neo.121024] [PMID: 23633918]
[43]
Kurig, B.; Shymanets, A.; Bohnacker, T. Ras is an indispensable coregulator of the class I B phosphoinositide 3-kinase p87/p110γ. Proceedings of the National Academy of Sciences, 2009, pp. 20312-7.
[44]
Mishra, R.; Patel, H.; Alanazi, S.; Kilroy, M.K.; Garrett, J.T. PI3K inhibitors in cancer: Clinical implications and adverse effects. Int. J. Mol. Sci., 2021, 22(7), 3464.
[http://dx.doi.org/10.3390/ijms22073464] [PMID: 33801659]
[45]
Yoshioka, K. Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking. Biochem. Soc. Trans., 2021, 49(2), 893-901.
[http://dx.doi.org/10.1042/BST20200835] [PMID: 33666217]
[46]
Merrill, N.M.; Schipper, J.L.; Karnes, J.B.; Kauffman, A.L.; Martin, K.R.; MacKeigan, J.P. PI3K- C2α knockdown decreases autophagy and maturation of endocytic vesicles. Donaldson JG, editor. PLOS ONE., 2017, 12(9), e0184909.
[47]
Gulluni, F.; De Santis, M.C.; Margaria, J.P.; Martini, M.; Hirsch, E. Class II PI3K functions in cell biology and disease. Trends Cell Biol., 2019, 29(4), 339-359.
[http://dx.doi.org/10.1016/j.tcb.2019.01.001] [PMID: 30691999]
[48]
Cisse, O.; Quraishi, M.; Gulluni, F.; Guffanti, F.; Mavrommati, I.; Suthanthirakumaran, M.; Oh, L.C.R.; Schlatter, J.N.; Sarvananthan, A.; Broggini, M.; Hirsch, E.; Falasca, M.; Maffucci, T. Downregulation of class II phosphoinositide 3-kinase PI3K-C2β delays cell division and potentiates the effect of docetaxel on cancer cell growth. J. Exp. Clin. Cancer Res., 2019, 38(1), 472.
[http://dx.doi.org/10.1186/s13046-019-1472-9] [PMID: 31752944]
[49]
Brown, W.J.; DeWald, D.B.; Emr, S.D.; Plutner, H.; Balch, W.E. Role for phosphatidylinositol 3-kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells. J. Cell Biol., 1995, 130(4), 781-796.
[http://dx.doi.org/10.1083/jcb.130.4.781] [PMID: 7642697]
[50]
Ellis, H.; Ma, C.X. PI3K inhibitors in breast cancer therapy. Curr. Oncol. Rep., 2019, 21(12), 110.
[http://dx.doi.org/10.1007/s11912-019-0846-7] [PMID: 31828441]
[51]
Fattahi, S.; Amjadi-Moheb, F.; Tabaripour, R.; Ashrafi, G.H.; Akhavan-Niaki, H. PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond. Life Sci., 2020, 262, 118513.
[http://dx.doi.org/10.1016/j.lfs.2020.118513] [PMID: 33011222]
[52]
Murugan, A.K. Special issue: PI3K/Akt signaling in human cancer. Semin. Cancer Biol., 2019, 59, 1-2.
[http://dx.doi.org/10.1016/j.semcancer.2019.10.022] [PMID: 31689493]
[53]
Colardo, M.; Segatto, M.; Di Bartolomeo, S. Targeting RTK-PI3K-mTOR Axis in gliomas: An update. Int. J. Mol. Sci., 2021, 22(9), 4899.
[http://dx.doi.org/10.3390/ijms22094899] [PMID: 34063168]
[54]
Bleeker, F.E.; Lamba, S.; Zanon, C.; Molenaar, R.J.; Hulsebos, T.J.M.; Troost, D.; van Tilborg, A.A.; Vandertop, W.P.; Leenstra, S.; van Noorden, C.J.F.; Bardelli, A. Mutational profiling of kinases in glioblastoma. BMC Cancer, 2014, 14(1), 718.
[http://dx.doi.org/10.1186/1471-2407-14-718] [PMID: 25256166]
[55]
Langhans, J.; Schneele, L.; Trenkler, N.; von Bandemer, H.; Nonnenmacher, L.; Karpel-Massler, G.; Siegelin, M.D.; Zhou, S.; Halatsch, M.E.; Debatin, K.M.; Westhoff, M.A. The effects of PI3K-mediated signalling on glioblastoma cell behaviour. Oncogenesis, 2017, 6(11), 398.
[http://dx.doi.org/10.1038/s41389-017-0004-8] [PMID: 29184057]
[56]
Zhang, Y.; Dube, C.; Gibert, M., Jr; Cruickshanks, N.; Wang, B.; Coughlan, M.; Yang, Y.; Setiady, I.; Deveau, C.; Saoud, K.; Grello, C.; Oxford, M.; Yuan, F.; Abounader, R. The p53 pathway in glioblastoma. Cancers., 2018, 10(9), 297.
[http://dx.doi.org/10.3390/cancers10090297] [PMID: 30200436]
[57]
Cantley, L.C. The phosphoinositide 3-kinase pathway. Science, 2002, 296(5573), 1655-1657.
[http://dx.doi.org/10.1126/science.296.5573.1655] [PMID: 12040186]
[58]
Westhoff, M.A.; Karpel-Massler, G.; Brühl, O.; Enzenmüller, S.; La Ferla-Brühl, K.; Siegelin, M.D.; Nonnenmacher, L.; Debatin, K.M. A critical evaluation of PI3K inhibition in glioblastoma and neuroblastoma therapy. Mol. Cell. Ther., 2014, 2(1), 32.
[http://dx.doi.org/10.1186/2052-8426-2-32] [PMID: 26056598]
[59]
Shahcheraghi, S.H.; Tchokonte-Nana, V.; Lotfi, M.; Lotfi, M.; Ghorbani, A.; Sadeghnia, H.R. Wnt/beta-catenin and PI3K/Akt/mTOR signaling pathways in glioblastoma: Two main targets for drug design: A review. Curr. Pharm. Des., 2020, 26(15), 1729-1741.
[http://dx.doi.org/10.2174/1381612826666200131100630] [PMID: 32003685]
[60]
Petővári, G.; Hujber, Z.; Krencz, I.; Dankó, T.; Nagy, N.; Tóth, F.; Raffay, R.; Mészáros, K.; Rajnai, H.; Vetlényi, E.; Takács-Vellai, K.; Jeney, A.; Sebestyén, A. Targeting cellular metabolism using rapamycin and/or doxycycline enhances anti-tumour effects in human glioma cells. Cancer Cell Int., 2018, 18(1), 211.
[http://dx.doi.org/10.1186/s12935-018-0710-0] [PMID: 30574020]
[61]
Chen, Z.X.; Wallis, K.; Fell, S.M.; Sobrado, V.R.; Hemmer, M.C.; Ramsköld, D.; Hellman, U.; Sandberg, R.; Kenchappa, R.S.; Martinson, T.; Johnsen, J.I.; Kogner, P.; Schlisio, S. RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma. Cancer Discov., 2014, 4(4), 434-451.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0362] [PMID: 24469107]
[62]
Ströbele, S.; Schneider, M.; Schneele, L.; Siegelin, M.D.; Nonnenmacher, L.; Zhou, S. A potential role for the inhibition of PI3K signaling in glioblastoma therapy. Castresana JS, editor. PLOS ONE., 2015, 10(6), e0131670.
[63]
Felsberg, J.; Hentschel, B.; Kaulich, K.; Gramatzki, D.; Zacher, A.; Malzkorn, B.; Kamp, M.; Sabel, M.; Simon, M.; Westphal, M.; Schackert, G.; Tonn, J.C.; Pietsch, T.; von Deimling, A.; Loeffler, M.; Reifenberger, G.; Weller, M. Epidermal growth factor receptor variant III (EGFRvIII) positivity in EGFR -amplified glioblastomas: Prognostic role and comparison between primary and recurrent tumors. Clin. Cancer Res., 2017, 23(22), 6846-6855.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0890] [PMID: 28855349]
[64]
Xie, S.; Ni, J.; McFaline-Figueroa, J.R.; Wang, Y.; Bronson, R.T.; Ligon, K.L.; Wen, P.Y.; Roberts, T.M.; Zhao, J.J. Divergent roles of PI3K isoforms in PTEN-deficient glioblastomas. Cell Rep., 2020, 32(13), 108196.
[http://dx.doi.org/10.1016/j.celrep.2020.108196] [PMID: 32997991]
[65]
Wang, H.; Xu, T.; Jiang, Y.; Xu, H.; Yan, Y.; Fu, D.; Chen, J. The challenges and the promise of molecular targeted therapy in malignant gliomas. Neoplasia, 2015, 17(3), 239-255.
[http://dx.doi.org/10.1016/j.neo.2015.02.002] [PMID: 25810009]
[66]
Le Rhun, E.; Preusser, M.; Roth, P.; Reardon, D.A.; van den Bent, M.; Wen, P.; Reifenberger, G.; Weller, M. Molecular targeted therapy of glioblastoma. Cancer Treat. Rev., 2019, 80, 101896.
[http://dx.doi.org/10.1016/j.ctrv.2019.101896] [PMID: 31541850]
[67]
Ou, A.; Yung, W.K.A.; Majd, N. Molecular mechanisms of treatment resistance in glioblastoma. Int. J. Mol. Sci., 2020, 22(1), 351.
[http://dx.doi.org/10.3390/ijms22010351] [PMID: 33396284]
[68]
Li, X.; Wu, C.; Chen, N.; Gu, H.; Yen, A.; Cao, L.; Wang, E.; Wang, L. PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma. Oncotarget., 2016, 7(22), 33440-33450.
[http://dx.doi.org/10.18632/oncotarget.7961] [PMID: 26967052]
[69]
Yang, J.; Nie, J.; Ma, X.; Wei, Y.; Peng, Y.; Wei, X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Mol. Cancer., 2019, 18(1), 26.
[http://dx.doi.org/10.1186/s12943-019-0954-x] [PMID: 30782187]
[70]
Sami, A.; Karsy, M. Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: novel therapeutic agents and advances in understanding. Tumour Biol., 2013, 34(4), 1991-2002.
[http://dx.doi.org/10.1007/s13277-013-0800-5] [PMID: 23625692]
[71]
Shergalis, A.; Bankhead, A.; Luesakul, U.; Muangsin, N.; Neamati, N. Current challenges and opportunities in treating glioblastoma. Pharmacol Rev., 2018, 70(3), 412-445.
[http://dx.doi.org/10.1124/pr.117.014944]
[72]
Hughes, J.P.; Rees, S.; Kalindjian, S.B.; Philpott, K.L. Principles of early drug discovery. Br. J. Pharmacol., 2011, 162(6), 1239-1249.
[http://dx.doi.org/10.1111/j.1476-5381.2010.01127.x] [PMID: 21091654]
[73]
Ediriweera, M.K.; Tennekoon, K.H.; Samarakoon, S.R. In vitro assays and techniques utilized in anticancer drug discovery. J. Appl. Toxicol., 2019, 39(1), 38-71.
[http://dx.doi.org/10.1002/jat.3658] [PMID: 30073673]
[74]
Kotecki, N.; Kindt, N.; Krayem, M.; Awada, A. New horizons in early drugs development in solid cancers. Curr. Opin. Oncol., 2021, 33(5), 513-519.
[http://dx.doi.org/10.1097/CCO.0000000000000766] [PMID: 34310410]
[75]
Atanasov, A.G.; Waltenberger, B.; Pferschy-Wenzig, E.M.; Linder, T.; Wawrosch, C.; Uhrin, P.; Temml, V.; Wang, L.; Schwaiger, S.; Heiss, E.H.; Rollinger, J.M.; Schuster, D.; Breuss, J.M.; Bochkov, V.; Mihovilovic, M.D.; Kopp, B.; Bauer, R.; Dirsch, V.M.; Stuppner, H. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv., 2015, 33(8), 1582-1614.
[http://dx.doi.org/10.1016/j.biotechadv.2015.08.001] [PMID: 26281720]
[76]
Yao, W.; Gong, H.; Mei, H.; Shi, L.; Yu, J.; Hu, Y. Taxifolin targets PI3K and mTOR and inhibits glioblastoma multiforme. J. Oncol., 2021, 20(2021), 1-12.
[77]
Thuan, N.H.; Shrestha, A.; Trung, N.T.; Tatipamula, V.B.; Van Cuong, D.; Canh, N.X.; Van Giang, N.; Kim, T.S.; Sohng, J.K.; Dhakal, D. Advances in biochemistry and the biotechnological production of taxifolin and its derivatives. Biotechnol. Appl. Biochem., 2022, 69(2), 848-861.
[http://dx.doi.org/10.1002/bab.2156] [PMID: 33797804]
[78]
Das, A.; Baidya, R.; Chakraborty, T.; Samanta, A.K.; Roy, S. Pharmacological basis and new insights of taxifolin: A comprehensive review. Biomed. Pharmacother., 2021, 142, 112004.
[http://dx.doi.org/10.1016/j.biopha.2021.112004] [PMID: 34388527]
[79]
Xie, J.; Pang, Y.; Wu, X. Taxifolin suppresses the malignant progression of gastric cancer by regulating the AhR/CYP1A1 signaling pathway. Int. J. Mol. Med., 2021, 48(5), 197.
[http://dx.doi.org/10.3892/ijmm.2021.5030] [PMID: 34490474]
[80]
Wang, R.; Zhu, X.; Wang, Q.; Li, X.; Wang, E.; Zhao, Q.; Wang, Q.; Cao, H. The anti-tumor effect of taxifolin on lung cancer via suppressing stemness and epithelial-mesenchymal transition in vitro and oncogenesis in nude mice. Ann. Transl. Med., 2020, 8(9), 590-0.
[http://dx.doi.org/10.21037/atm-20-3329] [PMID: 32566617]
[81]
Butt, S.S.; Khan, K.; Badshah, Y.; Rafiq, M.; Shabbir, M. Evaluation of pro-apoptotic potential of taxifolin against liver cancer. PeerJ, 2021, 9, e11276.
[http://dx.doi.org/10.7717/peerj.11276] [PMID: 34113483]
[82]
Li, J.; Hu, L.; Zhou, T.; Gong, X.; Jiang, R.; Li, H.; Kuang, G.; Wan, J.; Li, H. Taxifolin inhibits breast cancer cells proliferation, migration and invasion by promoting mesenchymal to epithelial transition via β-catenin signaling. Life Sci., 2019, 232, 116617.
[http://dx.doi.org/10.1016/j.lfs.2019.116617] [PMID: 31260685]
[83]
Su, R.Y.; Hsueh, S.C.; Chen, C.Y.; Hsu, M.J.; Lu, H.F.; Peng, S.F.; Chen, P.Y.; Lien, J.C.; Chen, Y.L.; Chueh, F.S.; Chung, J.G.; Yeh, M.Y.; Huang, Y.P. Demethoxycurcumin suppresses proliferation, migration, and Invasion of Human Brain Glioblastoma Multiforme GBM 8401 Cells via PI3K/Akt Pathway. Anticancer Res., 2021, 41(4), 1859-1870.
[http://dx.doi.org/10.21873/anticanres.14952] [PMID: 33813391]
[84]
Han, G.; Bi, R.; Le, Q.; Zhao, L.L.; Dong, Y.; Lin, Q.H. Study on effect of demethoxycurcumin in Curcuma long on stability of curcumin. Zhong Yao Cai, 2008, 31(4), 592-594.
[PMID: 18661836]
[85]
Hatamipour, M.; Ramezani, M.; Tabassi, S.A.S.; Johnston, T.P.; Ramezani, M.; Sahebkar, A. Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties. J. Cell. Physiol., 2018, 233(12), 9247-9260.
[http://dx.doi.org/10.1002/jcp.27029] [PMID: 30076727]
[86]
Hoxhaj, G.; Manning, B.D. The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nat. Rev. Cancer, 2020, 20(2), 74-88.
[http://dx.doi.org/10.1038/s41568-019-0216-7] [PMID: 31686003]
[87]
Jiang, H.; Shang, X.; Wu, H.; Gautam, S.C.; Al-Holou, S.; Li, C.; Kuo, J.; Zhang, L.; Chopp, M. Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells. J. Exp. Ther. Oncol., 2009, 8(1), 25-33.
[PMID: 19827268]
[88]
Clark, P.A.; Bhattacharya, S.; Elmayan, A.; Darjatmoko, S.R.; Thuro, B.A.; Yan, M.B.; van Ginkel, P.R.; Polans, A.S.; Kuo, J.S. Resveratrol targeting of AKT and p53 in glioblastoma and glioblastoma stem-like cells to suppress growth and infiltration. J. Neurosurg., 2017, 126(5), 1448-1460.
[http://dx.doi.org/10.3171/2016.1.JNS152077] [PMID: 27419830]
[89]
Debinski, W.; Tatter, S.B. Convection-enhanced delivery for the treatment of brain tumors. Expert Rev. Neurother., 2009, 9(10), 1519-1527.
[http://dx.doi.org/10.1586/ern.09.99] [PMID: 19831841]
[90]
Florean, C.; Dicato, M.; Diederich, M. Immune-modulating and anti-inflammatory marine compounds against cancer. Semin. Cancer Biol., 2022, 80, 58-72.
[http://dx.doi.org/10.1016/j.semcancer.2020.02.008] [PMID: 32070764]
[91]
Yao, Y.; Sun, S.; Cao, M.; Mao, M.; He, J.; Gai, Q.; Qin, Y.; Yao, X.; Lu, H.; Chen, F.; Wang, W.; Luo, M.; Zhang, H.; Huang, H.; Ju, J.; Bian, X.W.; Wang, Y. Grincamycin B functions as a potent inhibitor for glioblastoma stem cell via targeting RHOA and PI3K/AKT. ACS Chem. Neurosci., 2020, 11(15), 2256-2265.
[http://dx.doi.org/10.1021/acschemneuro.0c00206] [PMID: 32584547]
[92]
Wang, Z.; Li, Z.; Zhao, W.; Huang, H.; Wang, J.; Zhang, H.; Lu, J.; Wang, R.; Li, W.; Cheng, Z.; Xu, W.; Di Zhu; Zhou, L.; Jiang, W.; Yu, L.; Liu, J.; Luo, C.; Zhu, H.; Dan Ye; Pan, W.; Ju, J.; Dang, Y. Identification and characterization of isocitrate dehydrogenase 1 (IDH1) as a functional target of marine natural product grincamycin B. Acta Pharmacol. Sin., 2021, 42(5), 801-813.
[http://dx.doi.org/10.1038/s41401-020-0491-6] [PMID: 32796956]
[93]
Calvert, A.E.; Chalastanis, A.; Wu, Y.; Hurley, L.A.; Kouri, F.M.; Bi, Y.; Kachman, M.; May, J.L.; Bartom, E.; Hua, Y.; Mishra, R.K.; Schiltz, G.E.; Dubrovskyi, O.; Mazar, A.P.; Peter, M.E.; Zheng, H.; James, C.D.; Burant, C.F.; Chandel, N.S.; Davuluri, R.V.; Horbinski, C.; Stegh, A.H. Cancer-associated IDH1 promotes growth and resistance to targeted therapies in the absence of mutation. Cell Rep., 2017, 19(9), 1858-1873.
[http://dx.doi.org/10.1016/j.celrep.2017.05.014] [PMID: 28564604]
[94]
Pan, L.; Chai, H.; Kinghorn, A.D. The continuing search for antitumor agents from higher plants. Phytochem. Lett., 2010, 3(1), 1-8.
[http://dx.doi.org/10.1016/j.phytol.2009.11.005] [PMID: 20228943]
[95]
Gairola, K.; Gururani, S.; Bahuguna, A.; Garia, V.; Pujari, R.; Dubey, S.K. Natural products targeting cancer stem cells: Implications for cancer chemoprevention and therapeutics. J. Food Biochem., 2021, 45(7), e13772.
[http://dx.doi.org/10.1111/jfbc.13772] [PMID: 34028051]
[96]
Lathia, J.D.; Mack, S.C.; Mulkearns-Hubert, E.E.; Valentim, C.L.L.; Rich, J.N. Cancer stem cells in glioblastoma. Genes Dev., 2015, 29(12), 1203-1217.
[http://dx.doi.org/10.1101/gad.261982.115] [PMID: 26109046]
[97]
Biserova, K.; Jakovlevs, A.; Uljanovs, R.; Strumfa, I. Cancer stem cells: Significance in origin, pathogenesis and treatment of glioblastoma. Cells, 2021, 10(3), 621.
[http://dx.doi.org/10.3390/cells10030621] [PMID: 33799798]
[98]
Sonabend, A.M.; Carminucci, A.S.; Amendolara, B.; Bansal, M.; Leung, R.; Lei, L.; Realubit, R.; Li, H.; Karan, C.; Yun, J.; Showers, C.; Rothcock, R.; O, J.; Califano, A.; Canoll, P.; Bruce, J.N. Convection-enhanced delivery of etoposide is effective against murine proneural glioblastoma. Neuro-oncol., 2014, 16(9), 1210-1219.
[http://dx.doi.org/10.1093/neuonc/nou026] [PMID: 24637229]
[99]
Wang, Z.; Liang, P.; He, X.; Wu, B.; Liu, Q.; Xu, Z.; Wu, H.; Liu, Z.; Qian, Y.; Wang, S.; Zhu, R. Etoposide loaded layered double hydroxide nanoparticles reversing chemoresistance and eradicating human glioma stem cells in vitro and in vivo. Nanoscale, 2018, 10(27), 13106-13121.
[http://dx.doi.org/10.1039/C8NR02708K] [PMID: 29961791]
[100]
Needle, M.N.; Molloy, P.T.; Geyer, J.R.; Herman-Liu, A.; Belasco, J.B.; Goldwein, J.W.; Sutton, L.; Phillips, P.C. Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors. Med. Pediatr. Oncol., 1997, 29(1), 28-32.
[http://dx.doi.org/10.1002/(SICI)1096-911X(199707)29:1<28::AID-MPO5>3.0.CO;2-U] [PMID: 9142202]
[101]
Gimple, R.C.; Bhargava, S.; Dixit, D.; Rich, J.N. Glioblastoma stem cells: Lessons from the tumor hierarchy in a lethal cancer. Genes Dev., 2019, 33(11-12), 591-609.
[http://dx.doi.org/10.1101/gad.324301.119] [PMID: 31160393]
[102]
Wang, J.B.; Pan, H.X.; Tang, G.L. Production of doramectin by rational engineering of the avermectin biosynthetic pathway. Bioorg. Med. Chem. Lett., 2011, 21(11), 3320-3323.
[http://dx.doi.org/10.1016/j.bmcl.2011.04.008] [PMID: 21514826]
[103]
Gao, A.; Wang, X.; Xiang, W.; Liang, H.; Gao, J.; Yan, Y. Reversal of P-glycoprotein-mediated multidrug resistance in vitro by doramectin and nemadectin. J. Pharm. Pharmacol., 2010, 62(3), 393-399.
[http://dx.doi.org/10.1211/jpp.62.03.0016] [PMID: 20487225]
[104]
Chen, C.; Liang, H.; Qin, R.; Li, X.; Wang, L.; Du, S.; Chen, Z.; Meng, X.; Lv, Z.; Wang, Q.; Meng, J.; Gao, A. Doramectin inhibits glioblastoma cell survival via regulation of autophagy in vitro and in vivo. Int. J. Oncol., 2022, 60(3), 29.
[http://dx.doi.org/10.3892/ijo.2022.5319] [PMID: 35137919]
[105]
Wang, J.; Liu, X.; Hong, Y.; Wang, S.; Chen, P.; Gu, A.; Guo, X.; Zhao, P. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, exhibits antitumoral activity and induces autophagy in glioblastoma. J. Exp. Clin. Cancer Res., 2017, 36(1), 96.
[http://dx.doi.org/10.1186/s13046-017-0549-6] [PMID: 28716053]
[106]
Nadeem Abbas, M.; Kausar, S.; Wang, F.; Zhao, Y.; Cui, H. Advances in targeting the epidermal growth factor receptor pathway by synthetic products and its regulation by epigenetic modulators as a therapy for glioblastoma. Cells., 2019, 8(4), 350.
[http://dx.doi.org/10.3390/cells8040350] [PMID: 31013819]
[107]
Charmsaz, S.; Prencipe, M.; Kiely, M.; Pidgeon, G.; Collins, D. Innovative technologies changing cancer treatment. Cancers., 2018, 10(6), 208.
[http://dx.doi.org/10.3390/cancers10060208] [PMID: 29921753]
[108]
Bittlinger, M.; Bicer, S.; Peppercorn, J.; Kimmelman, J. Ethical considerations for phase I trials in oncology. J. Clin. Oncol., 2022, 40(30), 3474-3488.
[http://dx.doi.org/10.1200/JCO.21.02125] [PMID: 35275736]
[109]
Minneci, P.C.; Deans, K.J. Clinical trials. Semin. Pediatr. Surg., 2018, 27(6), 332-337.
[http://dx.doi.org/10.1053/j.sempedsurg.2018.10.003] [PMID: 30473036]
[110]
Mokhtari, R.B.; Homayouni, T.S.; Baluch, N.; Morgatskaya, E.; Kumar, S.; Das, B.; Yeger, H. Combination therapy in combating cancer. Oncotarget., 2017, 8(23), 38022-38043.
[http://dx.doi.org/10.18632/oncotarget.16723] [PMID: 28410237]
[111]
Lah, T.T.; Novak, M.; Pena Almidon, M.A.; Marinelli, O.; Žvar Baškovič, B.; Majc, B.; Mlinar, M.; Bošnjak, R.; Breznik, B.; Zomer, R.; Nabissi, M. Cannabigerol is a potential therapeutic agent in a novel combined therapy for glioblastoma. Cells, 2021, 10(2), 340.
[http://dx.doi.org/10.3390/cells10020340] [PMID: 33562819]
[112]
Ghosh, D.; Nandi, S.; Bhattacharjee, S. Combination therapy to checkmate Glioblastoma: Clinical challenges and advances. Clin. Transl. Med., 2018, 7(1), 33.
[http://dx.doi.org/10.1186/s40169-018-0211-8] [PMID: 30327965]
[113]
Yang, J.; Shi, Z.; Liu, R.; Wu, Y.; Zhang, X. Combined-therapeutic strategies synergistically potentiate glioblastoma multiforme treatment via nanotechnology. Theranostics., 2020, 10(7), 3223-3239.
[http://dx.doi.org/10.7150/thno.40298] [PMID: 32194864]
[114]
Speranza, M.C.; Nowicki, M.O.; Behera, P.; Cho, C.F.; Chiocca, E.A.; Lawler, S.E. BKM-120 (Buparlisib): A Phosphatidyl- inositol-3 kinase inhibitor with anti-invasive properties in glioblastoma. Sci. Rep., 2016, 6(1), 20189.
[http://dx.doi.org/10.1038/srep20189] [PMID: 26846842]
[115]
Chakravarti, A.; Zhai, G.; Suzuki, Y.; Sarkesh, S.; Black, P.M.; Muzikansky, A.; Loeffler, J.S. The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas. J. Clin. Oncol., 2004, 22(10), 1926-1933.
[http://dx.doi.org/10.1200/JCO.2004.07.193] [PMID: 15143086]
[116]
Wachsberger, P.R.; Lawrence, Y.R.; Liu, Y.; Rice, B.; Feo, N.; Leiby, B.; Dicker, A.P. Hsp90 inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma. J. Cancer Res. Clin. Oncol., 2014, 140(4), 573-582.
[http://dx.doi.org/10.1007/s00432-014-1594-6] [PMID: 24500492]
[117]
Hainsworth, J.D.; Becker, K.P.; Mekhail, T.; Chowdhary, S.A.; Eakle, J.F.; Wright, D.; Langdon, R.M.; Yost, K.J.; Padula, G.D.A.; West-Osterfield, K.; Scarberry, M.; Shaifer, C.A.; Shastry, M.; Burris, H.A., III; Shih, K. Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II). J. Neurooncol., 2019, 144(2), 303-311.
[http://dx.doi.org/10.1007/s11060-019-03227-7] [PMID: 31392595]
[118]
Wen, P.Y.; Rodon, J.A.; Mason, W.; Beck, J.T.; DeGroot, J.; Donnet, V.; Mills, D.; El-Hashimy, M.; Rosenthal, M. Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. ESMO Open, 2020, 5(4), e000673.
[http://dx.doi.org/10.1136/esmoopen-2020-000673] [PMID: 32661186]
[119]
Heffron, T.P.; Ndubaku, C.O.; Salphati, L.; Alicke, B.; Cheong, J.; Drobnick, J.; Edgar, K.; Gould, S.E.; Lee, L.B.; Lesnick, J.D.; Lewis, C.; Nonomiya, J.; Pang, J.; Plise, E.G.; Sideris, S.; Wallin, J.; Wang, L.; Zhang, X.; Olivero, A.G. Discovery of clinical development candidate GDC-0084, a brain penetrant inhibitor of PI3K and mTOR. ACS Med. Chem. Lett., 2016, 7(4), 351-356.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00005] [PMID: 27096040]
[120]
Salphati, L.; Alicke, B.; Heffron, T.P.; Shahidi-Latham, S.; Nishimura, M.; Cao, T.; Carano, R.A.; Cheong, J.; Greve, J.; Koeppen, H.; Lau, S.; Lee, L.B.; Nannini-Pepe, M.; Pang, J.; Plise, E.G.; Quiason, C.; Rangell, L.; Zhang, X.; Gould, S.E.; Phillips, H.S.; Olivero, A.G. Brain distribution and efficacy of the brain penetrant PI3K inhibitor GDC-0084 in orthotopic mouse models of human glioblastoma. Drug Metab. Dispos., 2016, 44(12), 1881-1889.
[http://dx.doi.org/10.1124/dmd.116.071423] [PMID: 27638506]
[121]
Wen, P.Y.; De Groot, J.F.; Battiste, J.D.; Goldlust, S.A.; Garner, J.S.; Simpson, J.A.; Kijlstra, J.; Olivero, A.; Cloughesy, T.F. Escalation portion of phase II study to evaluate the safety, pharmacokinetics, and clinical activity of the PI3K/mTOR inhibitor paxalisib (GDC-0084) in glioblastoma (GBM) with unmethylated O6-methylguanine-methyltransferase (MGMT) promotor status. J. Clin. Oncol., 2020, 38(S15), 2550-0.
[http://dx.doi.org/10.1200/JCO.2020.38.15_suppl.2550]
[122]
Przystal, J.M.; Cianciolo Cosentino, C.; Yadavilli, S.; Zhang, J.; Laternser, S.; Bonner, E.R.; Prasad, R.; Dawood, A.A.; Lobeto, N.; Chin Chong, W.; Biery, M.C.; Myers, C.; Olson, J.M.; Panditharatna, E.; Kritzer, B.; Mourabit, S.; Vitanza, N.A.; Filbin, M.G.; de Iuliis, G.N.; Dun, M.D.; Koschmann, C.; Cain, J.E.; Grotzer, M.A.; Waszak, S.M.; Mueller, S.; Nazarian, J. Imipridones affect tumor bioenergetics and promote cell lineage differentiation in diffuse midline gliomas. Neuro-oncol., 2022, 24(9), 1438-1451.
[http://dx.doi.org/10.1093/neuonc/noac041] [PMID: 35157764]
[123]
Chan, H.Y.; Choi, J.; Jackson, C.; Lim, M. Combination immunotherapy strategies for glioblastoma. J. Neurooncol., 2021, 151(3), 375-391.
[http://dx.doi.org/10.1007/s11060-020-03481-0] [PMID: 33611705]
[124]
Hörnschemeyer, J.; Kirschstein, T.; Reichart, G.; Sasse, C.; Venus, J.; Einsle, A.; Porath, K.; Linnebacher, M.; Köhling, R.; Lange, F. Studies on biological and molecular effects of small-molecule kinase inhibitors on human glioblastoma cells and organotypic brain slices. Life., 2022, 12(8), 1258.
[http://dx.doi.org/10.3390/life12081258] [PMID: 36013437]
[125]
Sweeney, C.; Bracarda, S.; Sternberg, C.N.; Chi, K.N.; Olmos, D.; Sandhu, S.; Massard, C.; Matsubara, N.; Alekseev, B.; Parnis, F.; Atduev, V.; Buchschacher, G.L., Jr; Gafanov, R.; Corrales, L.; Borre, M.; Stroyakovskiy, D.; Alves, G.V.; Bournakis, E.; Puente, J.; Harle-Yge, M.L.; Gallo, J.; Chen, G.; Hanover, J.; Wongchenko, M.J.; Garcia, J.; de Bono, J.S. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): A multicentre, randomised, double-blind, phase 3 trial. Lancet., 2021, 398(10295), 131-142.
[http://dx.doi.org/10.1016/S0140-6736(21)00580-8] [PMID: 34246347]
[126]
Dent, R.; Oliveira, M.; Isakoff, S.J.; Im, S.A.; Espié, M.; Blau, S.; Tan, A.R.; Saura, C.; Wongchenko, M.J.; Xu, N.; Bradley, D.; Reilly, S.J.; Mani, A.; Kim, S.B.; Lee, K.S.; Sohn, J.H.; Kim, J.H.; Seo, J.H.; Kim, J.S.; Park, S.; Velez, M.; Dakhil, S.; Hurvitz, S.; Valero, V.; Vidal, G.; Figlin, R.; Allison, M.A.K.; Chan, D.; Cobleigh, M.; Hansen, V.; Iannotti, N.; Lawler, W.; Salkini, M.; Seigel, L.; Romieu, G.; Debled, M.; Levy, C.; Hardy-Bessard, A.; Guiu, S.; Estevez, L.G.; Villanueva, R.; Martin, A.G.; Rovira, P.S.; Montaño, A.; Plaza, M.I.C.; Saenz, J.A.G.; Garau, I.; Bermejo, B.; Alonso, E.V.; Wang, H-C.; Huang, C-S.; Chen, S-C.; Chen, Y-H.; Tseng, L-M.; Wong, A.; Ang, C.S.P.; De Laurentiis, M.; Conte, P.F.; De Braud, F.; Montemurro, F.; Gianni, L.; Dirix, L. Final results of the double-blind placebo-controlled randomized phase 2 LOTUS trial of first-line ipatasertib plus paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer. Breast Cancer Res. Treat., 2021, 189(2), 377-386.
[http://dx.doi.org/10.1007/s10549-021-06143-5] [PMID: 34264439]
[127]
Kaley, T.J.; Panageas, K.S.; Pentsova, E.I.; Mellinghoff, I.K.; Nolan, C.; Gavrilovic, I.; DeAngelis, L.M.; Abrey, L.E.; Holland, E.C.; Omuro, A.; Lacouture, M.E.; Ludwig, E.; Lassman, A.B. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Ann. Clin. Transl. Neurol., 2020, 7(4), 429-436.
[http://dx.doi.org/10.1002/acn3.51009] [PMID: 32293798]
[128]
Galanis, E.; Buckner, J.C.; Maurer, M.J.; Kreisberg, J.I.; Ballman, K.; Boni, J.; Peralba, J.M.; Jenkins, R.B.; Dakhil, S.R.; Morton, R.F.; Jaeckle, K.A.; Scheithauer, B.W.; Dancey, J.; Hidalgo, M.; Walsh, D.J. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: A North Central Cancer Treatment Group Study. J. Clin. Oncol., 2005, 23(23), 5294-5304.
[http://dx.doi.org/10.1200/JCO.2005.23.622] [PMID: 15998902]
[129]
Almeida Pachioni, J.D.; Magalhães, J.G.; Cardoso Lima, E.J.; Moura Bueno, L.D.; Barbosa, J.F.; Malta de Sá, M.; Rangel-Yagui, C.O. Alkylphospholipids - a promising class of chemotherapeutic agents with a broad pharmacological spectrum. J. Pharm. Pharm. Sci., 2013, 16(5), 742-759.
[http://dx.doi.org/10.18433/J3CW23] [PMID: 24393556]
[130]
Pitter, K.L.; Galbán, C.J.; Galbán, S.; Saeed-Tehrani, O.; Li, F.; Charles, N. Perifosine and CCI 779 co-operate to induce cell death and decrease proliferation in PTEN-Intact and PTEN-Deficient PDGF-Driven Murine Glioblastoma. PLoS ONE., 2011, 6(1), e14545.
[131]
Kaley, T.J.; Panageas, K.S.; Mellinghoff, I.K.; Nolan, C.; Gavrilovic, I.T.; DeAngelis, L.M.; Abrey, L.E.; Holland, E.C.; Lassman, A.B. Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. J. Neurooncol., 2019, 144(2), 403-407.
[http://dx.doi.org/10.1007/s11060-019-03243-7] [PMID: 31325145]
[132]
Chinnaiyan, P.; Won, M.; Wen, P.Y.; Rojiani, A.M.; Wendland, M.; Dipetrillo, T.A.; Corn, B.W.; Mehta, M.P. RTOG 0913: A phase 1 study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. Int. J. Radiat. Oncol. Biol. Phys., 2013, 86(5), 880-884.
[http://dx.doi.org/10.1016/j.ijrobp.2013.04.036] [PMID: 23725999]
[133]
Chinnaiyan, P.; Won, M.; Wen, P.Y.; Rojiani, A.M.; Werner-Wasik, M.; Shih, H.A.; Ashby, L.S.; Michael Yu, H.H.; Stieber, V.W.; Malone, S.C.; Fiveash, J.B.; Mohile, N.A.; Ahluwalia, M.S.; Wendland, M.M.; Stella, P.J.; Kee, A.Y.; Mehta, M.P. 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.
[http://dx.doi.org/10.1093/neuonc/nox209] [PMID: 29126203]
[134]
O’Reilly, K.E.; Rojo, F.; She, Q.B.; Solit, D.; Mills, G.B.; Smith, D.; Lane, H.; Hofmann, F.; Hicklin, D.J.; Ludwig, D.L.; Baselga, J.; Rosen, N. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res., 2006, 66(3), 1500-1508.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2925] [PMID: 16452206]
[135]
Luchman, H.A.; Stechishin, O.D.M.; Nguyen, S.A.; Lun, X.Q.; Cairncross, J.G.; Weiss, S. Dual mTORC1/2 blockade inhibits glioblastoma brain tumor initiating cells in vitro and in vivo and synergizes with temozolomide to increase orthotopic xenograft survival. Clin. Cancer Res., 2014, 20(22), 5756-5767.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-3389] [PMID: 25316808]
[136]
Lapointe, S.; Mason, W.; MacNeil, M.; Harlos, C.; Tsang, R.; Sederias, J.; Luchman, H.A.; Weiss, S.; Rossiter, J.P.; Tu, D.; Seymour, L.; Smoragiewicz, M. A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme: A CCTG study. Invest. New Drugs, 2020, 38(4), 1137-1144.
[http://dx.doi.org/10.1007/s10637-019-00875-4] [PMID: 31707687]
[137]
Osuka, S.; Van Meir, E.G. Overcoming therapeutic resistance in glioblastoma: the way forward. J. Clin. Invest., 2017, 127(2), 415-426.
[http://dx.doi.org/10.1172/JCI89587] [PMID: 28145904]
[138]
Arrillaga-Romany, I.; Chi, A.S.; Allen, J.E.; Oster, W.; Wen, P.Y.; Batchelor, T.T. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. Oncotarget, 2017, 8(45), 79298-79304.
[http://dx.doi.org/10.18632/oncotarget.17837] [PMID: 29108308]
[139]
Mecca, C; Giambanco, I; Donato, R; Arcuri, C. Targeting mTOR in glioblastoma: Rationale and preclinical/clinical evidence. Dis Markers, 2018, 2018, 9230479.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy