A number of molecular therapeutic agents, derived from exploiting our knowledge 
of the oncogenic pathways that are frequently deregulated in cancer, are now 
entering clinical trials. One of these is the novel agent 
17-allylamino-17-demethoxygeldanamycin that acts to inhibit the hsp90 molecular 
chaperone. Treatment of four human colon cancer cell lines with iso-effective 
concentrations of this agent resulted in depletion of c-raf-1 and akt and 
inhibition of signal transduction. We have used gene expression array analysis 
to identify genes responsive to treatment with this drug. The expression of 
hsp90 client protein genes was not affected, but hsc hsp70, hsp90beta, keratin 
8, keratin 18 and caveolin-1 were deregulated following treatment. These 
observations were consistent with inhibition of signal transduction and 
suggested a possible mechanism of resistance or recovery from 
17-allylamino-17-demethoxygeldanamycin treatment. The results shed light on the 
molecular mode of action of the hsp90 inhibitors, and suggest possible molecular 
markers of drug action for use in hypothesis testing clinical trials. Oncogene 
(2000) 19, 4125 - 4133