Resurrecting Tumor Suppressors to Combat Cancer

The human body is prone to developing cancer, from a very early stage of life, until the end of life. The human genome has several built in tumor suppressor genes, whose protein products suppress the formation of tumors. It is important for these tumor suppressor genes to continue expressing their tumor suppressor proteins as long as the person lives. Over time, DNA can be damaged or altered, leading to loss of function of these protective genes. One way these genes can lose their ability to make protective proteins is through methylation.

Methylation is the gradual addition of chemical units known as methyl groups to genes, and as these groups accumulate, the gene gradually shuts down. Some drugs prevent the methylation process, releasing the gene to produce its tumor suppressor. In fact, methylation is a salient characteristic of cancer cells, and can be used as a biomarker for cancer.

Fortunately, researchers are developing new drugs called "hypomethylating agens" that have the ability to remove the methyl groups and restore function to tumor suppressor genes. This Bio.com report discusses one of these new drugs:

The drug, decitabine, is designed to turn on genes that cancer had switched off, and in this study, patients who were treated with it achieved a significantly higher overall response rate, compared to patients receiving supportive care, which includes transfusions of red blood cells and platelets.

Results of the randomized Phase III clinical trial, published March 13, 2006 in the online version of the journal Cancer, also concluded that in treated patients who responded to the drug, the median time to progression of the disease, or death, was 17.5 months, compared to 9.8 months in patients who did not.

"This is a very promising drug that we believe works even better when patients use it for a period that is longer than that tested in this trial," says lead author, Hagop Kantarjian, M.D., chair of the Department of Leukemia at M. D. Anderson.

....Decitabine is a "biological disease modifier" that was given fast-track approval by the Food and Drug Administration in April 2003.

It is a DNA hypomethylating agent that fights cancer by reversing a chemical process (methylation) that turns off tumor-suppressor genes that protect cells from becoming cancerous.

Other hypomethylating agents are being used and developed for several other types of malignancy including leukemia and breast cancer.

These drugs work by turning back time, as it were--gene time. Other drugs are being developed to turn back time for the entire genome. It is a race against the clock, but then, it always has been.