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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Idle Hands | Main | The Bigger They Are »

October 8, 2002

Genetic Optimism

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Posted by Derek

he genetic news of the day, subject of good-sized headlines in the Wall St. Journal and elsewhere, is an upcoming paper in PNAS on a candidate cancer gene called DBC2. Some of these abbreviations are pretty recondite, but not this one - it stands for "Deleted in Breast Cancer," which is pretty tame by the standards of genomic nomenclature.

These researchers (at Cold Spring Harbor) have looked at a lot of different cell lines, and they've spent years tracking everything down. This gene seems to be altered in a number of breast and lung cancers, and (equally importantly) doesn't seem to be changed in normal tissue samples. There's a reasonable chance that DBC mutations are indeed a causative factor in some of these cancers, and the evidence is good enough to put a lot more people working on it (which is no doubt happening as we speak.) Still, this would be a good time for everyone to recite the Pharmacogenomics Pledge. All together now, especially you folks at New Scientist:

Correlation Does Not Imply Causation

I singled out the New Scientist article because of lines like this one, from their article:

"Hamaguchi thinks treatments based on switching on the gene, dubbed DBC2, could be available in three or four years."

If he really said that, then I hate to be the bearer of bad news: he's almost certainly wrong. Even if they found such a treatment this afternoon, it would take more time than that to make it available. Development, testing, full-scale clinical trials, regulatory scrutiny - it really adds up.

And that's after the hard part, finding the treatment. The problem is, switching on an individual gene isn't something that we're really good at - we tend to switch a few hundred others on (and switch a few hundred others off) when we try that via drug therapy. (And keep in mind that this gene is defective in many cancer cell lines, so presumably switching it on won't do much good in those cases.) This sounds like a possible candidate for gene therapy, but how to apply that to solid tumors is a non-trivial question.

If it were a question of switching the gene off, there would be some hope from either an antisense DNA approach (not that it's easy to get that to work - no drug has made it yet, despite years of effort,) or through a very interesting new technique called RNA interference. That needs to be the subject of another posting entirely, but it's potentially promising - for turning things off, that is.

As the press articles generally make clear, no one knows what the actual function of DBC2 is. It's from somewhere in the wilderness of chromosome 8, and it seems to be from a family of proteins about which almost nothing is known. It doesn't look like a typical cell-surface receptor, nor like the usual classes of enzymes. I'll go out on a limb and guess it's some sort of transcription factor, but that's a pretty broad category.

The real accomplishment of this work is finding the gene, not finding ways to use it. Good new drug targets are getting harder to find, as is becoming painfully clear these days, and a whole new potential class of them is a welcome development. Figuring out what they might be is bound to lead to some useful information. Let's hope it leads to a drug, too - but it's going to be more than four years before that happens, I'm sad to say.

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