[extropy-chat] HEALTH: Cancer - step by step

[Robert J. Bradbury]

As the Three Stooges once pointed out:

"Slowly I turned... Step by Step... Inch by Inch..."

Recently Hoffmann-La Roche scientists have demonstrated
molecules that may interfere with the MDM2 gene product
which in turn interferes with the action of p53 in
cancerous cells.  (p53 is considered one of the genome
guardians that normally would promote cells that are
cancerous committing suicide.)

See:
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2.
Vassilev, L. T., et al. Science 2 Jan 2004 (Epub).

Abstract:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14704432&dopt=Abstract

> MDM2 binds the p53 tumor suppressor protein with high affinity and
> negatively modulates its transcriptional activity and stability.
> Overexpression of MDM2, found in many human tumors, effectively impairs
> p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and
> may offer a novel strategy for cancer therapy. Here we identify potent
> and selective small-molecule antagonists of MDM2 and confirm their mode
> of action through crystal structures of complexes. These compounds bind
> MDM2 in the p53-binding pocket and activate the p53 pathway in cancer
> cells, leading to cell cycle arrest, apoptosis and growth inhibition of
> human tumor xenografts in nude mice.

This is a good example of how cancer will be conquered at the molecular
level.

Robert