Molecular cancer, 2017-06, Vol.16 (1), p.100-16, Article 100
2017
Details
- Autor(en) / Beteiligte
- Titel
- Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development
- Ist Teil von
- Molecular cancer, 2017-06, Vol.16 (1), p.100-16, Article 100
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- SpringerLink (Online service)
- Beschreibungen/Notizen
- Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism. Numerous PI3K inhibitors including pan-PI3K, isoform-selective and dual PI3K/mammalian target of rapamycin (mTOR) inhibitors have exhibited favorable preclinical results and entered clinical trials in a range of hematologic malignancies and solid tumors. Furthermore, combination of inhibitors targeting PI3K and other related pathways may exert synergism on suppressing tumor growth and improving patients' prognosis. Currently, only a handful of PI3K inhibitors are in phase I/II clinical trials for GBM treatment. In this review, we focus on the importance of PI3K/Akt pathway in GBM, and summarize the current development of PI3K inhibitors alone or in combination with other inhibitors for GBM treatment from preclinical to clinical studies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1476-4598eISSN: 1476-4598DOI: 10.1186/s12943-017-0670-3Titel-ID: cdi_doaj_primary_oai_doaj_org_article_c98705bd36474511bea033bc6bd3f4ff
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT protein, Alkylation, Angiogenesis, Animals, Antineoplastic Agents - administration & dosage, Antineoplastic Agents - adverse effects, Antineoplastic Agents - chemistry, Antineoplastic Agents - therapeutic use, Antineoplastic Combined Chemotherapy Protocols - adverse effects, Antineoplastic Combined Chemotherapy Protocols - therapeutic use, Apoptosis, Brain cancer, Brain Neoplasms - drug therapy, Brain Neoplasms - metabolism, Brain Neoplasms - mortality, Brain Neoplasms - pathology, Care and treatment, Catalysis, Cell growth, Cell survival, Cellular signal transduction, Central nervous system, Clinical Studies as Topic, Clinical trials, Deoxyribonucleic acid, DNA, DNA methylation, Drug Discovery, Drug Evaluation, Preclinical, Drugs, Epidermal growth factor, GBM, Genetic aspects, Glioblastoma, Glioblastoma - drug therapy, Glioblastoma - metabolism, Glioblastoma - mortality, Glioblastoma - pathology, Glioblastoma multiforme, Humans, Inhibitors, Isoenzymes, Kinases, Ligands, Medical prognosis, Metabolism, Molecular Targeted Therapy, Motility, mTOR, Mutation, Phosphatase, Phosphatidylinositol 3-Kinases - antagonists & inhibitors, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation, PI3K, Plasma, Prognosis, Protein Kinase Inhibitors - administration & dosage, Protein Kinase Inhibitors - adverse effects, Protein Kinase Inhibitors - therapeutic use, Protein synthesis, Proteins, Proto-Oncogene Proteins c-akt - metabolism, Rapamycin, Review, Signal transduction, Signal Transduction - drug effects, Solid tumors, Synergism, Temozolomide, TOR protein, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - metabolism, Treatment Outcome, Tumors