This morning a MM listserv member reported on something that he has been taking for the past two months called cyclopamine. I’d never heard of it before, or perhaps hadn’t paid any attention to it, so I looked it up. Well, this may be one of the most exciting things I have read about in recent times. I still have some (a lot of?) research to do, but I thought I would post some preliminary findings. I still have to read all of the following studies carefully when I have more time. Not today.

The remarkable story of how cyclopamine was discovered can be read in the following 2005 article published in Forbes: http://tinyurl.com/yu6df5 In a nutshell: in the 1940s and 50s, one-eyed lambs were being born on a farm in Idaho. During an 11-year investigation conducted by the U.S. Dept. of Agriculture, it was discovered that the farm’s sheep were grazing in fields of corn lilies, flowers that contain a poison (later called cyclopamine ) that does not harm adult animals but does cause birth defects. The Forbes article provides many more details, also about how cyclopamine later came to be of interest to cancer research. Fascinating. Cyclopamine was found to inhibit a gene known as Sonic hedgehog, which is involved in the process of adult stem cell division and apparently is crucial for the development of MM, pancreatic cancer and other cancers. For more info on the importance of hedgehog pathways and MM and other B-cell malignancies, please see this July 2007 study: http://tinyurl.com/2g6kk6.

A team of researchers at Johns Hopkins made the connections between cyclopamine, the Idaho lambs and the hedgehog gene. Their findings were published in 2002 in Genes and Development (http://tinyurl.com/38vppa). A few years later, in 2006, a Stanford study published in PNAS tells us that the hedgehog signalling (or Hh) pathway is crucial for the proliferation of MM stem cells. Well, lo and behold, cyclopamine inhibits that pathway: http://tinyurl.com/2hx5yd.

As I mentioned, I have been able to glance only at the conclusions of all these studies, but plan to read them carefully soon. My time has run out, but I did want to post quickly about this bit of extraordinary news. If we can get rid of our cancer-making stem cells, we can kill off the remaining cancer cells with curcumin or resveratrol or whatnot. How about that? A couple of final questions (and this is another reason why I need to do more research!): how come cyclopamine targets only cancer stem cells? Why doesn’t it target non-cancerous stem cells as well?