title: Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme.
abstract: Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single anti-angiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.
authors.affiliation: Biomedical Center, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic.|Department of Histology and Embryology, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Polivka
authors.affiliation: Department of Neurology, Faculty of Medicine in Plzen, Charles University, Faculty Hospital Plzen, Plzen, Czech Republic polivka@fnplzen.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Polivka
authors.affiliation: Biomedical Center, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic.
authors.forename: Lubos
authors.initials: L
authors.lastname: Holubec
authors.affiliation: Biomedical Center, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic.|Department of Histology and Embryology, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Kubikova
authors.affiliation: Department of Neurosurgery, Faculty of Medicine in Plzen, Charles University, Czech Republic and Faculty Hospital Plzen, Plzen, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Priban
authors.affiliation: Department of Pathology, Faculty of Medicine in Plzen, Charles University, and Faculty Hospital Plzen, Plzen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
authors.affiliation: Department of Pathology, Faculty of Medicine in Plzen, Charles University, and Faculty Hospital Plzen, Plzen, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Pivovarcikova
authors.affiliation: Department of Surgery, Faculty of Medicine in Plzen, Charles University, and Faculty Hospital Plzen, Plzen, Czech Republic.
authors.forename: Inka
authors.initials: I
authors.lastname: Treskova
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000639:trends*; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000639:trends*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors
keywords: CTLA4 inhibition; GBM; Glioblastoma multiforme; PD1 inhibition; clinical trials; immune checkpoint inhibitors; immunotherapy; personalized medicine; review; targeted therapy