G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma: the old, the new, and the future

Author(s)

Castro-Gamero, Angel Mauricio ^[1] ; Pezuk, Julia Alejandra ^{[2, 3]} ; Brassesco, Maria Sol ^[4] ; Tone, Luiz Gonzaga ^{[5, 6]}

Affiliation

^[1] Fed Univ Alfenas UNIFAL MG, Inst Nat Sci, Human Genet Lab, BR-37130001 Alfenas - Brazil

^[2] Anhanguera Univ Sao Paulo UNIAN SP, Biotechnol & Innovat Hlth Program, BR-05145200 Sao Paulo - Brazil

^[3] Anhanguera Univ Sao Paulo UNIAN SP, Pharm Program, BR-05145200 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Biol, Fac Philosophy Sci & Letters Ribeirao Preto, BR-14040901 Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pediat, BR-14049900 Ribeirao Preto - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Genet, BR-14049900 Ribeirao Preto - Brazil

• Document type: Review article
• Source: CANCER BIOLOGY & MEDICINE; v. 15, n. 4, p. 354-374, NOV 2018.
• Web of Science Citations: 1

Abstract

Glioblastoma (GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. In this context, we review promising ongoing and future strategies for GBM therapeutics aimed towards G2/M inhibition such as anti-microtubule agents and targeted therapy against G2/M regulators like cyclin-dependent kinases, Aurora inhibitors, PLK1, BUB, 1, and BUBR1, and survivin. Moreover, we also include investigational agents in the preclinical and early clinical settings. Although several drugs were shown to be gliotoxic, most of them have not yet entered therapeutic trials. The use of either single exposure or a combination with novel compounds may lead to treatment alternatives for GBM patients in the near future. (AU)

• FAPESP's process: 12/16888-8 - Effects of tetra-O-methyl nordihydroguaiaretic acid in glioblastoma: a combined transcriptomic and proteomic study
• Grantee: Luiz Gonzaga Tone
• Support Opportunities: Regular Research Grants