Linked Life Data

18058572

Source:http://linkedlifedata.com/resource/pubmed/id/18058572

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-12-6
pubmed:abstractText
High-grade primary brain tumors remain refractory to conventional treatment approaches, including radiotherapy and cytotoxic chemotherapy. Molecular neuro-oncology has now begun to clarify the transformed phenotype of these malignant tumors and identify oncogenic pathways that might be amenable to small-molecule and antibody 'targeted' therapy. Growth factor signaling pathways are often upregulated in these tumors and contribute to oncogenesis through autocrine and paracrine mechanisms. Excessive growth factor receptor stimulation can also lead to overactivity of the downstream Ras signaling pathway. Other internal signal transduction pathways that may become dysregulated during transformation include Raf, MEK, PI3K, Akt (protein kinase B), and mTOR (mammalian target of rapamycin). In addition, overactivity of VEGF and other effectors leads to neoplastic angiogenesis. 'Targeted' therapy against the growth factor signaling and Ras pathways include tyrosine kinase inhibitors (eg, imatinib and erlotinib) and farnesyltransferase inhibitors (eg, tipifarnib). Molecular therapeutic small molecules specific to Raf, PI3K, and mTOR include sorafenib, LY-294002, and temsirolimus, respectively. 'Targeted' anti-angiogenesis approaches include mAbs to VEGF (eg, bevacizumab) and VEGF receptor tyrosine kinase inhibitors (eg, vatalanib and sunitinib). Further development of 'targeted' therapies designed to modulate the activity of these pathways, and evaluation of these new agents in clinical trials, will be needed to improve survival and quality-of-life for patients with malignant brain tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1472-4472
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1009-21
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18058572-Angiogenesis Inhibitors, pubmed-meshheading:18058572-Antibodies, Monoclonal, pubmed-meshheading:18058572-Antineoplastic Agents, pubmed-meshheading:18058572-Brain Neoplasms, pubmed-meshheading:18058572-Clinical Trials as Topic, pubmed-meshheading:18058572-Enzyme Inhibitors, pubmed-meshheading:18058572-Forecasting, pubmed-meshheading:18058572-Genes, ras, pubmed-meshheading:18058572-Humans, pubmed-meshheading:18058572-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:18058572-Molecular Structure, pubmed-meshheading:18058572-Neovascularization, Pathologic, pubmed-meshheading:18058572-Phosphatidylinositol 3-Kinases, pubmed-meshheading:18058572-Protein Kinase Inhibitors, pubmed-meshheading:18058572-Receptor, Epidermal Growth Factor, pubmed-meshheading:18058572-Signal Transduction, pubmed-meshheading:18058572-Sirolimus, pubmed-meshheading:18058572-Treatment Outcome
pubmed:year
2007
pubmed:articleTitle
Small-molecule and antibody approaches to molecular chemotherapy of primary brain tumors.
pubmed:affiliation
Dardinger Neuro-Oncology Center, Division of Neuro-Oncology, 465 Means Hall, 1654 Upham Drive, Columbus, OH 43210, USA. newton.12@osu.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural