Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Dec 25, 2016Anticancer research

New Developments in Precision Treatments and Immune-Based Therapy for Glioblastoma Brain Cancer

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Abstract

Median overall survival for patients with glioblastoma multiforme (GBM) is no longer than 15 months.

GBM is characterized by intense invasiveness and high resistance to treatment.
Standard therapies include surgery, radiotherapy, and chemotherapy with temozolomide, which are largely ineffective.
Progress in understanding GBM has identified various genetic and epigenetic alterations affecting cellular signaling and the tumor environment.
Only bevacizumab has received approval as an anti-angiogenic treatment for recurrent GBM in the USA and Canada.
Clinical trials are currently exploring the potential of immune checkpoint inhibitors for GBM treatment.
Recent randomized clinical trials have shown a relative lack of success for some targeted therapies and immunotherapies.

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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.

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Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Abstract

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