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

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.

Polivka J Jr ，Polivka J ，Holubec L ，Kubikova T ，Priban V ，Hes O ，Pivovarcikova K ，Treskova I ... -  《-》

New molecularly targeted therapies for glioblastoma multiforme.

Polivka J Jr ，Polivka J ，Rohan V ，Topolcan O ，Ferda J ... -  《-》

Topics in chemotherapy, molecular-targeted therapy, and immunotherapy for newly-diagnosed glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and it is associated with poor survival. The standard therapy for newly-diagnosed GBM is radiotherapy with concurrent temozolomide following maximal surgical resection. To improve the outcome of these patients, combinations of the standard therapy plus molecular-targeted agents have been tested in clinical trials. However, the addition of gefitinib to the standard therapy did not appear to improve clinical outcome, and the standard therapy plus bevacizumab showed no improvement in overall survival, although a 4-month improvement in progression-free survival (PFS) was observed. Phase II data have indicated the potential efficacy of talampanel combined with the standard therapy for patients with newly-diagnosed GBM, and these findings are awaiting validation in phase III trials. In addition, phase II trials have demonstrated that adjuvant immunotherapy is effective and tolerable for treatment of patients with GBM. In this article, we discuss topics in chemotherapy, molecular-targeted therapy, and immunotherapy for patients with newly-diagnosed GBM.

Okonogi N ，Shirai K ，Oike T ，Murata K ，Noda SE ，Suzuki Y ，Nakano T ... -  《-》

[What's next in glioblastoma treatment: Tumor-targeted or immune-targeted therapies?].

Glioblastoma (GBM) is associated with a poor prognosis. This review will discuss different directions of treatment, mostly regarding immunotherapies and combinatorial approaches. Standard treatment for newly diagnosed GBM is maximal and safe surgical resection followed by concurrent radiochemotherapy (RCT) based on temozolomide, allowing 14.6 months median survival. Nowadays, no combination with molecular-targeted therapy had significantly improved prognosis. Phases I and II data are emerging, highlighting the potential efficacy of associations with other therapies. Studies have suggested the potential of targeting tumor stem cells, at less partially responsible for resistance to RCT. There is now some evidence that immunotherapy is also relevant for brain tumors. Treatment strategies have mainly explored vaccines strategies, such as the dendritic cell, heat shock protein or EGFRvIII vaccines. Of the work initiated in melanoma, immune checkpoints inhibitors have exhibited stimulating results. Others trials have demonstrated potential of autologous stimulated lymphocytes. Moreover, strong data indicates that radiation therapy has the potential to promote immunogenicity and create a sort of in situ personalized vaccine. These data provide strong evidence to support the potential of associating combinatorial targeted and/or immunotherapeutic regimens in patients with GBM that may change patient outcome.

Schernberg A ，Marabelle A ，Massard C ，Armand JP ，Dumont S ，Deutsch E ，Dhermain F ... -  《-》

Current Immunotherapies for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include maximal safe surgical resection, radiation, and chemotherapy and are mostly limited by low therapeutic efficiency correlated with poor prognosis. Immunotherapy, which predominantly focuses on peptide vaccines, dendritic cell vaccines, chimeric antigen receptor T cells, checkpoint inhibitor therapy, and oncolytic virotherapy, have achieved some promising results in both preclinical and clinical trials. The future of immune therapy for GBM requires an integrated effort with rational combinations of vaccine therapy, cell therapy, and radio- and chemotherapy as well as molecule therapy targeting the tumor microenvironment.

Huang B ，Li X ，Li Y ，Zhang J ，Zong Z ，Zhang H ... -  《Frontiers in Immunology》