siRNA, NMD, and tumor antigen expression in cancer

A research team at the University of Miami has come up with an innovative new method that (please note the emphasis) might offer a completely new way to eliminate remaining cancer cells in patients with prostate and other types of cancer after first-line therapy.

Pastor et al. have published a report in  Nature suggesting that it may be possible to stimulate the cancer cells to express a higher concentration of tumor antigens (the peptide molecules that trigger defensive activity by the human immune system). If this works, it ought to result in a higher probability that the patient’s immune system would identify and eliminate the remaining tumor cells floating around in the blood stream and the lymphatic system of patients who had received curative therapy. (Another good article on this research for the layman appeared in the Miami Herald yesterday.)

The research conducted by Pastor and colleagues so far has shown only that is is possible — in the laboratory — to inhibit so-called “nonsense-mediated messenger RNA decay” (NMD) through the use of small interfering RNA (siRNA) molecules. Such inhibition of NMD in tumor cells led to the expression of new antigens and their immune-mediated rejection. And the researchers were able to actually eliminate certain types of tumor cells in rats.

In theory, it might become possible to treat a man with Gleason 7 prostate cancer with curative intent, and then to use specific siRNA molecules to increase the expression of tumor antigens on prostate cancer cells left behind after first-line treatment. The more highly expressed tumor antigens might then be more efficiently attacked and eliminated — along with the rest of the prostate cancer cells they are attached to — by the patients normal immune processes.

Now it will take many years to develop and test a hypothesis like this, but it is research of this type that may really be able to lead toward prevention of (the all too common) biochemical relapse that can occur months or even years after first-line therapy for what appears to be localized prostate cancer. It is currently estimated that, each year, tens of thousands of patients in America have a biochemical relapse after first-line therapy for apparently localized prostate cancer. If we could eliminate the progression of prostate cancer in even 25 percent of those patients it would have a huge impact on the quality and perhaps the quantity of life of these patients.

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