Glioblastoma Multiforme: An Overview of Emerging Therapeutic Targets

Taylor, Olivia; Brzozowski, Joshua S.; Skelding, Kathryn A.

doi:10.3389/fonc.2019.00963

Cited by 249 publications

(203 citation statements)

References 106 publications

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“…As classified by the World Health Organization (WHO), glioblastoma (GBM) is a highly malignant grade IV astrocytoma accounting for approximately 50% of all gliomas [ 2 , 3 , 4 ]. Although GBM has an incidence of less than 10 per 100,000, it is incurable; thus, the burden of disease on patients and carers remains significant, resulting in an average loss of 12 years of life [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Radiation and Temozolomide-Induced Glioblastoma Invadopodia Activity Using Ion Channel Drugs

Dinevska

Gazibegovic

Morokoff

et al. 2020

Cancers

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Glioblastoma (GBM) is the most prevalent and malignant type of primary brain cancer. The rapid invasion and dissemination of tumor cells into the surrounding normal brain is a major driver of tumor recurrence, and long-term survival of GBM patients is extremely rare. Actin-rich cell membrane protrusions known as invadopodia can facilitate the highly invasive properties of GBM cells. Ion channels have been proposed to contribute to a pro-invasive phenotype in cancer cells and may also be involved in the invadopodia activity of GBM cells. GBM cell cytotoxicity screening of several ion channel drugs identified three drugs with potent cell killing efficacy: flunarizine dihydrochloride, econazole nitrate, and quinine hydrochloride dihydrate. These drugs demonstrated a reduction in GBM cell invadopodia activity and matrix metalloproteinase-2 (MMP-2) secretion. Importantly, the treatment of GBM cells with these drugs led to a significant reduction in radiation/temozolomide-induced invadopodia activity. The dual cytotoxic and anti-invasive efficacy of these agents merits further research into targeting ion channels to reduce GBM malignancy, with a potential for future clinical translation in combination with the standard therapy.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Radiation and Temozolomide-Induced Glioblastoma Invadopodia Activity Using Ion Channel Drugs

Dinevska

Gazibegovic

Morokoff

et al. 2020

Cancers

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“…Glioblastoma is the most aggressive primary malignant brain tumor, with a median survival of approximately 10 months [141]. It can be classified as primary (de novo) or secondary when glioblastoma derives from low-grade tumors [142].…”

Section: Glioblastomamentioning

confidence: 99%

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Ceci

Atzori

Lacal

et al. 2020

IJMS

175

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The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.

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“…The pharmacological treatment of glioblastoma (GBM) remains one of the hardest challenges in cancer precision therapy. An increasing volume of genetic data has clarified that GBM tumors present with multiple and diverse genetic aberrations in receptor tyrosine kinase (RTK), p53, and other pathways (Brennan et al, 2013;Taylor et al, 2019). Despite these advances, current therapy is based on a combination of surgery, radiation, and temozolomide, resulting in a median survival of 14.6 months, of which a mere 2.5 months are attributed to the chemotherapy (Stupp et al, 2005).…”

Section: Introductionmentioning

confidence: 99%