Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-kappa

[Rich66]

1: Nat Rev Drug Discov. (javascript:AL_get(this, 'jour', 'Nat Rev Drug Discov.');) 2008 Dec;7(12):1031-40.http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-logo_nrdd.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3094&itool=AbstractPlus-def&uid=19043452&db=pubmed&url=http://dx.doi.org/10.1038/nrd2759) <SCRIPT language=JavaScript1.2><!-- var Menu19043452 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Compound (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pccompound&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pccompound_mesh&LinkReadableName=Compound%20(MeSH%20Keyword)&IdsFromResult=19043452&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""], ["Substance (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pcsubstance&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pcsubstance_mesh&LinkReadableName=Substance%20(MeSH%20Keyword)&IdsFromResult=19043452&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=19043452&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus&ordinalpos=1' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=19043452&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""] ] --></SCRIPT>Links (javascript:PopUpMenu2_Set(Menu19043452);)
<DD class=abstract>
Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-kappaB pathways.

<!--AuthorList-->Dey A (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Dey%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Tergaonkar V (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Tergaonkar%20V%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Lane DP (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lane%20DP%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Laboratory of Cell Cycle Control, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore.
The p53 and nuclear factor-kappaB (NF-kappaB) pathways play crucial roles in human cancer, in which inactivation of p53 and hyperactivation of NF-kappaB is a common occurrence. Activation of p53 and inhibition of NF-kappaB promotes apoptosis. Although drugs are being designed to selectively activate p53 or inhibit NF-kappaB, there is no concerted effort yet to deliberately make drugs that can simultaneously do both. Recent results suggest that a surprising selection of small molecules have this desirable dual activity. In this Review we describe the principles behind such dual activities, describe the current candidate molecules and suggest mechanisms and approaches to their further development.
PMID: 19043452 [PubMed - indexed for MEDLINE]
</DD>

[Rich66]

http://www.wistar.org/tech_transfer/technologies/tech4.html

Novel Variants of p53 Tumor Suppressor Protein
Inventor: Thanos Halazonetis
Tech ID: HT-9500, HT-98001, HT-9436
Description: Inactivation of the p53 tumor suppressor protein, by mutation or by viruses, has been identified in over one-half of all human tumors. The inactivated protein usually has reduced DNA-binding capacity, which renders it ineffective in regulating cell division and cell growth. Delivery of the p53 gene to tumor cells has led to the elimination of the tumor in both animal models and some early clinical studies. One limitation of p53 gene therapy is that many tumors express high levels of the inactive mutant p53 protein, which can form complexes with and inactivate the normal protein that is introduced during therapy.
Wistar researchers have developed several p53 variants that have increased potency relative to the normal protein.

[Ellie F]

Thanks Rich
Again really exciting stuff. I hope they hurry up and develop this treatment. i was interested about deactivation of p53 as I received a vaccination for polio as a child and a few years ago read some research that highlighted that some batches of this given in the late 1950's and 1960's may have damaged this gene.
May not be relevant but you never know.
Ellie