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May 10, 2010
Malcolm Gladwell on Synta and Oncology
Posted by Derek
The folks at the New Yorker sent along this link to a new article by Malcolm Gladwell about Synta and their attempts to get elesclomol (STA-4783) to work as a melanoma therapy. (If you don't know how this one turns out, you might want to read the article before clicking on that second link).
Update: didn't realize that the full article was subscriber-only at the New Yorker site. Not sure if there's anything to be done about that, but I've dropped them a line. . .
Gladwell (an occasional reader of this blog) often takes some hits from experts in the fields he writes about, but after reading the article this morning, I think he's done a fine job of showing what drug discovery is like. His division between screening and rational drug design is a bit too sharply defined, to my eyes, but he gets all the important stuff right - namely, just how hard a business this is, how much luck is involved, and how much we don't know. Those are messages that a lot of people need to hear, and I hope that this piece helps get them out to a wide audience.
Comments (7)
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1. RandDChemist on May 10, 2010 8:36 AM writes...
One description of medicinal chemistry I've recently seen is calling it "an informed art". Quite apt.
Would this make people want to go back to placing a significant emphasis on large numbers or compounds?
"In the fields of observation chance favors only the prepared mind." Louis Pasteur
Permalink to Comment2. Sally on May 10, 2010 10:34 AM writes...
Hah, we must have received the same outreach and posted around the same time.
It was a good general description of cancer drug discovery, but they don't really exist in isolation - you need both for really great drugs that make a lasting impact to emerge. Screening is useful once you have a valid and viable target to hit based on extensive molecular biology research. Both Gleevec and Herceptin are examples of this synergy.
That said, what Gladwell missed was what really limits most drugs in cancer research is the heterogeneity of the disease.
Permalink to Comment3. Bob in FWB, FL on May 10, 2010 11:57 AM writes...
Re. your request to the New Yorker. Let us know if they move it outside the "paid access only" area or some such - that will prove the power of The Pipeline!
Permalink to Comment4. befuddled on May 10, 2010 3:46 PM writes...
@Sally, #2:
Certainly the heterogeneity of cancer is a big problem, but there are some targets/pathways which are important in a large fraction of cancers (like p53).
My impression is that the real problem is poor model systems. I believe most in vivo research has been done with human cancer cell lines implanted in immunodeficient mice. I'm actually surprised that those kind of studies have resulted in *anything* clinically useful.
Permalink to Comment5. sally on May 11, 2010 9:48 AM writes...
#4 Befuddled (lovely moniker BTW)
The challenge is that some targets and pathways like p53 and PTEN end up overexpressed in many cancers as a consequence of say, drug resistance, so blocking them doesn't have much effect. It's more a case of what else could be targeted to prevent/slow down the resistance developing in the first place.
There is some really interesting research going on right now looking at multiple combinations such as blocking PI3k-mTOR and the RAS-ERK pathway or the IGF-1R-EGFR with a MEKi together to reduce cross-talk, feedback/feedfoward loops etc.
The theory is that reduce the escape mechanisms for the cancer cells will reduce drug resistance and a rise in p53 or PTEN, which are indicators of that happening.
Permalink to Comment6. RandDChemist on May 11, 2010 10:03 AM writes...
Here's the WSJ take on the Gladwell article:
http://blogs.wsj.com/health/2010/05/10/gladwell-digs-into-cancer-drug-research-difficulties/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+wsj%2Fhealth%2Ffeed+%28WSJ.com%3A+Health+Blog%29&mod=smallbusiness
http://bit.ly/aGe8Om
Permalink to Comment7. Rogermunie on May 16, 2010 10:37 AM writes...
Gladwell's article is available on his website.
http://www.gladwell.com/pdf/treatment.pdf
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