A depressing post from Derek Lowe that sounds all too plausible:

We may be thinking about this the wrong way, though. For many years now, there have been people looking at genetic instability in tumor cells. (See this post from 2002 - yes, this blog has been around that long!) If this is a major component of the cancerous phenotype, it means that we could well have trouble with a target-by-target approach. (See this post by Robert Langreth at Forbes for a more recent take). And here's a PubMed search - as you can see, there's a lot of literature in this field, and a fair amount of controversy, too.

That would, in fact, mean that cancer shares something with infectious disease, and not, unfortunately, the era of the 1940s when the bacteria hadn't figured out what we could do to them yet. No, what it might mean is that many tumors might be made of such heterogeneous, constantly mutating cells that no one targeted approach will have a good chance of knocking them down sufficiently. Since that's exactly what we see, this is a hypothesis worth taking seriously.

Drug discovery is hard enough even before you add these sorts of challenges.  We've been spoiled by the last fifty years; the targets we have now are harder, and even the targets we thought we'd beaten are making a comeback.

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