Corante

About this Author
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

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
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

« Looking Back at the Genome | Main | California vs. Nature »

June 14, 2010

Angiotensin Receptor Blockers and Cancer: For Real?

Email This Entry

Posted by Derek

Well, this could be nothing, or it could be big trouble: there's a report out that taking the angiotensin antagonists (the various "sartans") might be linked to increase risk of cancer. A meta-analysis of several large trials, reported in Lancet Oncology, patients in the treatment groups showed a 7.2% incidence of new cancer diagnoses, versus 6% for the control groups. These are large sample sizes, so that difference has a p-value of 0.016.

The authors wisely refuse to take the data any further, and call for more investigation, which certainly seems warranted. The whole renin-angiotensin system is certainly involved in angiogenesis, and thus could very plausibly have effects in oncology. But the surprising thing is that there's evidence that blockade of the receptors could actually cut down on tumor formation, too. If you'd taken a survey last week, you'd probably have gotten a lot of people to bet that these drugs would actually have a protective effect.

So what's going on? It's going to be quite a while before we find out. But an awful lot of people take these drugs, and now they're all wondering what to do. . .

Comments (9) + TrackBacks (0) | Category: Cancer | Cardiovascular Disease


COMMENTS

1. chucky on June 14, 2010 11:22 AM writes...

Most likely noise, meta-analyses such as these mostly worthless....

Permalink to Comment

2. hypnos on June 14, 2010 12:07 PM writes...

Perhapt not too surprising, the vendor of the drug strongly disagrees with the results:

http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2010/14_june_2010_.html

Permalink to Comment

3. anchor on June 14, 2010 12:49 PM writes...

Derek: When people live longer, we all do get some type of cancer anyway. Did the study considered this preposition?

Permalink to Comment

4. LeeH on June 14, 2010 12:56 PM writes...

If it's true, I guess you'll have to do some sort of benefit/risk analysis. If it's a wash, then we're back to low tech solutions for blood pressure.

Permalink to Comment

5. partial agonist on June 14, 2010 4:50 PM writes...

Probably they will be protective vs. some genotypes of cancer while conferring a measurable added risk vs. other kinds of cancer, with the net sum being non-zero. So I guess it depends upon whether you are otherwise in a risk group for a particular type of cancer. sort of like the drugs affecting estrogen, a mixed bag.

For example if all of the added risk is in testicular and prostate cancer, maybe you are concerned about giving these to men, unless the benefit is huge and the patient can be regularly screened for those cancers.

Permalink to Comment

6. NHR_GUY on June 14, 2010 9:32 PM writes...

I am familiar with ARBs and Telmisartan in particular. Telmisartan is well known to have a measurable amount of (in vitro and in vivo) activity at PPAR gamma, an NHR used for insulin sensitization. PPAR gamma is the same biological target for the TZD's such as rosiglitazone and pioglitazone. I wonder if the acitivity at PPAR gamma is what could be driving this slight increase in cancer risk. Two points, the types of cancer being reported have been linked to PPAR gamma though the marketed drugs are ostensibly clean. From my experience, the other ARB's have no measurable PPAR gamma activity and FTA, did not show an increased cancer risk.

and a p.s.
the two year carc studies mandated by the FDA for all new PPAR's in development was the last nail in the coffin for big pharma working on PPAR's.

Permalink to Comment

7. alex on June 15, 2010 3:49 AM writes...

Surprisingly, its not only cancer. Meanwhile the FDA is conducting a safety review of olmesartan (Daiichi Sankyo) after determining that diabetic patients taking the drug in two completed phase 3 trials may have had an excess risk of cardiovascular death.

Permalink to Comment

8. Kent G. Budge on June 15, 2010 10:35 AM writes...

"the two year carc studies mandated by the FDA for all new PPAR's in development was the last nail in the coffin for big pharma working on PPAR's."

Given that pioglitazone is associated with a *decrease* in cardiovascular risk, I find this profoundly regrettable. There could be considerable value in figuring out why some PPAR agonists increase cardiovascular risk and others decrease it.

My suspicion is that there are subtle differences in how much a given glitazone sensitizes different tissues to insulin. Perhaps rosiglitazone sensitizes arterial walls to insulin more than it sensitizes skeletal muscle, causing the arterial walls to take up too much glucose, while pioglitazone sensitizes skeletal muscles a bit more and avoids this effect. But it looks like we'll never know now.

Permalink to Comment

9. Erock on June 2, 2011 12:29 PM writes...

Looks like the FDA can out-meta-analyze the Lancet. Nothing to see here... move along...

http://j.mp/kAvrps

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
Gitcher SF5 Groups Right Here
Changing A Broken Science System
One and Done
The Latest Protein-Protein Compounds
Professor Fukuyama's Solvent Peaks
Novartis Gets Out of RNAi
Total Synthesis in Flow
Sweet Reason Lands On Its Face