An experimental drug employed in a strudy at Mayo Clinic, to test the drug's efficacy to treat the fatal form of thyroid cancer, is found to halt the cancer cell growth by turning on the tumor supressor gene, which is otherwise turned off in cancer cells.
According to the researchers, few other cancer drugs have this property.
Describing their study in the journal Cancer Research, the researchers said that RS5444, being tested in a Phase 1/2 clinical trial to treat anaplastic thyroid cancer, might be useful for treating other cancers.
The agent is also known as CS-7017, according to their report.
Previous studied had already shown that RS5444 binds to a protein known as PPAR-gamma, a transcriptional factor that increases the expression of many genes.
The researchers said that past research had shown that human anaplastic thyroid tumour cells treated with RS5444 expressed a protein known as p21, which inhibited cell replication and tumour growth.
However, they added, the underlying factor behind that effect was unknown.
The team claimed that they had discovered that the agent actually forces PPAR-gamma to turn on the RhoB tumour suppressor gene, which in turn induces p21 expression.
"This is very unusual. Drugs typically target genes and proteins that are over-expressed and turn them off. We found that RS5444 turns on a valuable tumour suppressor gene. We rarely find a drug that can take a suppressed gene and cause it to be re-expressed," says the study's lead investigator, Dr. John Copland, a cancer biologist at the Mayo Clinic campus at Jacksonville.
Study co-author Dr. Robert Smallridge, who treats thyroid cancer patients at Mayo Clinic in Jacksonville, says that the finding suggests that other cancers in which RhoB is deactivated might respond to RS5444 or to similar drugs.
"This study provides a hint that this class of drugs could have a significant effect on cancer biology because of its action on this tumour suppressor gene," says Dr. Smallridge.
Dr. Copland adds: "RS5444 and other so-called PPAR-gamma drugs, which were originally created to treat diabetes because they help regulate glucose metabolism, are in development or being tested as cancer therapies. Taken orally, RS5444 requires 1,000-fold less dosage than current Food and Drug Administration-approved drugs in this class of compounds to inhibit tumor growth."
The researchers have been seeking to identify and characterize the molecular mechanisms underlying the cause and progression of human anaplastic thyroid carcinoma, and their goal is to develop effective molecular targeted therapies.