Linked Life Data

18054518

Source:http://linkedlifedata.com/resource/pubmed/id/18054518

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-2-4
pubmed:abstractText
The increased incidence of malignant melanoma in the last decades, its high mortality and pronounced therapy resistance pose an enormous challenge. Important therapeutic targets for melanoma are the induction of apoptosis and suppression of survival pathways. Preclinical studies have demonstrated the efficacy of pro-apoptotic Bcl-2 proteins and of death receptor ligands to trigger apoptosis in melanoma cells. In the clinical setting, BH3 domain mimics and death receptor agonists are therefore considered as promising, specific novel treatments to add to the conventional pro-apoptotic strategies such as chemo- or radiotherapy. However, constitutively activated survival pathways, in particular the mitogen-activated protein kinases, protein kinase B/Akt and nuclear factor (NF)-kappaB, all may work in concert to prevent effective therapy. Thus, selective biologicals developed with the aim to inhibit pro-survival signaling are currently tested in melanoma. For highly therapy-resistant tumors such as melanoma, development of novel drug combinations will be essential, and combinations of survival inhibitors and pro-apoptotic mediators appear most promising. The challenge of the near future will be to make a rational choice of the multiple possible combinations and protocols. This review gives a critical overview of proteins involved in melanoma chemoresistance, which are targets for current drug development leading to the best choice for future trials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1532-2084
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
218-34
pubmed:meshHeading
pubmed-meshheading:18054518-Animals, pubmed-meshheading:18054518-Antineoplastic Agents, pubmed-meshheading:18054518-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:18054518-Apoptosis, pubmed-meshheading:18054518-Caspases, pubmed-meshheading:18054518-Cell Survival, pubmed-meshheading:18054518-Cysteine Proteinase Inhibitors, pubmed-meshheading:18054518-Drug Resistance, Neoplasm, pubmed-meshheading:18054518-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18054518-Humans, pubmed-meshheading:18054518-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:18054518-Melanoma, pubmed-meshheading:18054518-Mutation, pubmed-meshheading:18054518-Protein Kinase Inhibitors, pubmed-meshheading:18054518-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:18054518-Receptors, Death Domain, pubmed-meshheading:18054518-Signal Transduction, pubmed-meshheading:18054518-Tumor Suppressor Protein p53
pubmed:year
2007
pubmed:articleTitle
Overcoming apoptosis deficiency of melanoma-hope for new therapeutic approaches.
pubmed:affiliation
Charité-Universitätsmedizin Berlin, Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany. juergen.eberle@charite.de
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't