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...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.展开更多
Background:Aurora kinases(AURKs)family plays a vital role not only in cell division but also in tumorigenesis.However,there are still rare systematic analyses of the diverse expression patterns and prognostic value of...Background:Aurora kinases(AURKs)family plays a vital role not only in cell division but also in tumorigenesis.However,there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer(BC).Systematic bioinformatics analysis was conducted to explore the biological role,prognostic value,and immunologic function of AURKs family in BC.Methods:The expression,prognostic value,and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals:ONCOMINE Gene Expression Profiling Interactive Analysis,Kaplan-Meier plotter,cBioPortal,Metascape,GeneMANIA,and LinkedOmics;and the result was verified using human tissues.Results:The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage(all P<0.05).BC patients with high AURKA and AURKB expression had a worse overall survival,relapse-free survival,and distant metastasisfree survival(all P<0.05).Verification experiment revealed that AURKA and AURKB were upregulated in BC(P<0.05).AURKA and AURKB were specifically associated with several tumor-associated kinases(polo-like kinase 1 and cyclin-dependent kinase 1),miRNAs(miR-507 and miR-381),and E2F transcription factor 1.Moreover,AURKA and AURKB were correlated with immune cell infiltration.Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway,platinum drug resistance signaling pathway,ErbB signaling pathway,Hippo signaling pathway,and nucleotide-binding and oligomerization domain-like receptor signaling pathway.Conclusions:Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.展开更多
基金supported by The Sao Paulo Research Foundation–FAPESP(Grant No.12/16888-8 and 2009/50118-2)
文摘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.
基金supported by grants from the National Natural Science Foundation of China(No.81703032)Natural Science Foundation of Hubei Province(No.2019CFB501)CSCO-Hengrui Cancer Research Fund(Y-HR2018-342).
文摘Background:Aurora kinases(AURKs)family plays a vital role not only in cell division but also in tumorigenesis.However,there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer(BC).Systematic bioinformatics analysis was conducted to explore the biological role,prognostic value,and immunologic function of AURKs family in BC.Methods:The expression,prognostic value,and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals:ONCOMINE Gene Expression Profiling Interactive Analysis,Kaplan-Meier plotter,cBioPortal,Metascape,GeneMANIA,and LinkedOmics;and the result was verified using human tissues.Results:The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage(all P<0.05).BC patients with high AURKA and AURKB expression had a worse overall survival,relapse-free survival,and distant metastasisfree survival(all P<0.05).Verification experiment revealed that AURKA and AURKB were upregulated in BC(P<0.05).AURKA and AURKB were specifically associated with several tumor-associated kinases(polo-like kinase 1 and cyclin-dependent kinase 1),miRNAs(miR-507 and miR-381),and E2F transcription factor 1.Moreover,AURKA and AURKB were correlated with immune cell infiltration.Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway,platinum drug resistance signaling pathway,ErbB signaling pathway,Hippo signaling pathway,and nucleotide-binding and oligomerization domain-like receptor signaling pathway.Conclusions:Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.
