Chemotherapy and immunotherapy of malignant glioma: molecular mechanisms and clinical perspectives.
Despite the considerable progress in modern tumor therapy, the prognosis for patients with glioblastoma, the most frequent malignant brain tumor, has not been substantially improved. Although cytoreductive surgery and radiotherapy are the mainstays of treatment for malignant glioma at present, novel cytotoxic drugs and immunotherapeutic approaches hold great promise as effective weapons against these malignancies. Thus, great efforts are being made to enhance antitumoral efficacy by combining various cytotoxic agents, by novel routes of drug administration, or by combining anticancer drugs and immune modulators. Immunotherapeutic approaches include cytotoxic cytokines, targeted antibodies, and vaccination strategies. However, the success of most of these experimental therapies is prevented by the marked molecular resistance of glioma cells to diverse cytotoxic agents or by glioma-associated immunosuppression. One promising experimental strategy to target glioma is the employment of death ligands such as CD95 (Fas/Apo1) ligand or Apo2 ligand (TRAIL). Specific proapoptotic approaches may overcome many of the obvious obstacles to a satisfactory management of malignant brain tumors.
Roth
W
W
Department of Neurology, University of Tübingen, School of Medicine, Germany.
Weller
M
M
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D001812:Blood-Brain Barrier / Q000276:immunology; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000494:pharmacology / Q000627:therapeutic use; D004358:Drug Therapy; D053222:Fas Ligand Protein; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D011878:Radiotherapy; D053221:TNF-Related Apoptosis-Inducing Ligand; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination
D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha