Wednesday, February 20, 2013

The Mystery of the Rancher's Affliction: Tracking Epigenetic Cancer

From Kalorama's Epigenetics Analyst, K. John Morrow, PhD: 

"Years ago I collaborated with a hematologist, Dr. Philip Periman, in Amarillo Texas, whose research interest was multiple myeloma. He saw a lot of patients with this disease; at that time (15 years ago) it was a death sentence, although it could be held at bay for some years. He was struck by its high incidence in ranchers and farmers in the Texas panhandle. Exposure to pesticides and other farm chemicals was long suggested as a risk factor. Recent work provides an explanation: these chemicals are epimutagens, myeloma appears to be an “epigenetic cancer” and it can be successfully treated with drugs that block methylation of cancer-causing genes.

Pomalidomide and lenalidomide are FDA-approved derivatives of thalidomide. They are slight modifications of the original thalidomide molecule, which achieved beneficial results, but also caused unpleasant side effects. When given to patients with multiple myeloma, they block the methylation of the gene p21WAF . This proceeds through a modification of the chromatin structure of this region, so when unmethylated, the p21WAF gene product is synthesized. This protein is a potentcyclin-dependent kinase inhibitor which functions as a regulator of the cell cycle. The end result is a self-destructive cascade resulting in the death of the tumor cells. These drugs have been so successful that they have kept myeloma patients alive for years, as reported recently by NPR (

So the picture of cause and effect looks clear. Pesticides and other epimutagenic compounds methylate suicide genes, shutting them off, so cells lose control of division. This results in cancers such as myeloma which can be destroyed by reactivating the suicide pathways through drugs that cause demethylation.  In the years to come we will see this as a recurrent theme in the origins and treatment of many different cancers. "

Kalorama Information's Epigenetics Market Research Report, authored by K. John Morrow, PhD, contains a full analysis of treatments and tests for epigenetics, including relevant companies and market sizes and forecasts.  The report  is available for purchase at