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 (http://www.npr.org/blogs/health/2013/02/18/172098789/targeted-cancer-drugs-keep-myeloma-patients-up-and-running).
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
