Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies.
Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient's tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG.
Thaker
Nikhil G
NG
Doris Duke Clinical Research Fellow, Departments of Neurosurgery, Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. thakerng@umdnj.edu
Pollack
Ian F
IF
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D006655:Histone Deacetylases