Current and emerging molecular targets in glioma

Rafael Roesler Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil. [email protected]; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil. [email protected]; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil

André T Brunetto Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil

Ana Lucia Abujamra Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Children’s Cancer Institute and Pediatric Oncology Unit, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Children’s Cancer Institute and Pediatric Oncology Unit, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil

Caroline Brunetto de Farias Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Children’s Cancer Institute and Pediatric Oncology Unit, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Children’s Cancer Institute and Pediatric Oncology Unit, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil

Algemir Lunardi Brunetto Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Children’s Cancer Institute and Pediatric Oncology Unit, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Children’s Cancer Institute and Pediatric Oncology Unit, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil

Gilberto Schwartsmann Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil

Abstract

Gliomas are the most common and lethal neurological cancers. Despite research efforts, the prognosis for patients with malignant gliomas remains poor. Advances in the understanding of cellular and molecular alterations in gliomas have led to the emergence of experimental molecularly targeted therapies. This article summarizes recent progress in the development of targeted therapies for glioma, focusing on emerging molecular targets, including neuropeptide and neurotrophin pathways, glutamate receptors, epigenetic mechanisms and glioma stem cell targets. Recent clinical trials of small molecules and antibodies targeted at growth factor pathways and intracellular signaling cascades are also discussed.

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Financial & competing interests disclosure

This research was supported by the National Council for Scientific and Technological Development (CNPq; grant number 303703/2009-1 to Rafael Roesler), the National Institute for Translational Medicine (INCT-TM), the South American Office for Anticancer Drug Development, and the Children’s Cancer Institute (ICI-RS). Rafael Roesler is a cofounder, partner and board member of NeuroAssay Ltd, has served as a consultant to Eurofarma, and has been remunerated for travel expenses by Janssen-Cilag. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Current and emerging molecular targets in glioma

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