Current status of clinical trials for glioblastoma.
Glioblastoma, the most highly aggressive and lethal form of brain cancer, has been a particular challenge to treat in terms of improving a patient's quality of life and outcome. Each of the current treatment options is limited due to factors intrinsic to the tumor's biology and the special microenvironment of its location within the brain. Surgical resection is limited by the non-circumscribed borders that can be detected. Radiation therapy has to contend with neurotoxicity to adjacent normal tissues. Chemotherapy is constrained by the blood-brain barrier, which is a very real constraint of systemic therapy -- producing minimal benefit with substantial toxicity in order to administer therapeutic dosages. In part, such hurdles explain the reasons why survival has changed little over many decades of research in this field. The newest generation of treatments includes more effective cytotoxic agents, so-called targeted compounds, and biologics/immunotherapeutics. This article summarizes the preclinical proof-of-concept research and human studies involving some of the agents creating the most positive buzz in the medical community. The advantages and limitations of each are described.
Salgaller
Michael L
ML
Toucan Capital Corp, Bethesda, MD 20814, USA. msalgaller@toucancapital.com
Liau
Linda M
LM
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides; D001672:Biocompatible Materials / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D019496:Cancer Vaccines / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003652:Decanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D000068877:Imatinib Mesylate; D000922:Immunotoxins / Q000627:therapeutic use; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D010879:Piperazines / Q000627:therapeutic use; D011091:Polyesters / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011506:Proteins; D011743:Pyrimidines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D000077204:Temozolomide; D014157:Transcription Factors / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001549:Benzamides; D001672:Biocompatible Materials; D019496:Cancer Vaccines; D003652:Decanoic Acids; D000922:Immunotoxins; D046912:Multiprotein Complexes; D010879:Piperazines; D011091:Polyesters; D047428:Protein Kinase Inhibitors; D011506:Proteins; D011743:Pyrimidines; D011799:Quinazolines; D014157:Transcription Factors; C401859:temsirolimus; D003606:Dacarbazine; D000068877:Imatinib Mesylate; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; D000069347:Erlotinib Hydrochloride; D051231:Farnesyltranstransferase; D066246:ErbB Receptors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D000077156:Gefitinib; D020123:Sirolimus; D000077204:Temozolomide