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MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

ABSTRACT: Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment.

SUBMITTER: Shea A

PROVIDER: S-EPMC4971921 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

Shea Amanda A Harish Varsha V Afzal Zainab Z Chijioke Juliet J Kedir Habib H Dusmatova Shahnoza S Roy Arpita A Ramalinga Malathi M Harris Brent B Blancato Jan J Verma Mukesh M Kumar Deepak D

Cancer medicine 20160610 8

Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of tar ...[more]

PMID: 27282910

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Project description:BackgroundGlioblastoma multiforme is a malignant intracranial neoplasm that constitutes a therapeutic challenge because of the associated high morbidity and mortality given the lack of effective approved medication and aggressive nature of the tumor. However, there has been extensive research recently to address the reasons implicated in the resistant nature of the tumor to pharmaceutical compounds, which have resulted in several clinical trials investigating promising treatment approaches.MethodsWe reviewed literature published since 2010 from PUBMED and several annual meeting abstracts through 15 September 2020. Selected articles included those relevant to topics of glioblastoma tumor biology, original basic research, clinical trials, seminal reviews, and meta-analyses. We provide a discussion based on the collected evidence regarding the challenging factors encountered during treatment, and we highlighted the relevant trials of novel therapies including immunotherapy and targeted medication.ResultsSelected literature revealed four main factors implicated in the low efficacy encountered with investigational treatments which included: (1) blood-brain barrier; (2) immunosuppressive microenvironment; (3) genetic heterogeneity; (4) external factors related to previous systemic treatment that can modulate tumor microenvironment. Investigational therapies discussed in this review were classified as immunotherapy and targeted therapy. Immunotherapy included: (1) immune checkpoint inhibitors; (2) adoptive cell transfer therapy; (3) therapeutic vaccines; (4) oncolytic virus therapy. Targeted therapy included tyrosine kinase inhibitors and other receptor inhibitors. Finally, we provide our perspective on future directions in treatment of glioblastoma.ConclusionDespite the limited success in development of effective therapeutics in glioblastoma, many treatment approaches hold potential promise including immunotherapy and novel combinational drugs. Addressing the molecular landscape and resistant immunosuppressive nature of glioblastoma are imperative in further development of effective treatments.

Dataset Information

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

Publications

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

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