More research reported at the recent Prostate Cancer Research Foundationmeeting that may impact the treatment of prostate cancer and possibly breast cancer also.
Lead researcher William Nelson, M.D., Ph.D., Professor of Oncology and Urology at the Johns Hopkins Kimmel Cancer Center, explained the findings. “One of the proteins in the cell that triggers this process is called a methyl-CpG binding protein, or MBD. We have discovered an antagonist of MBD2 that keeps this protein from binding to methylated genes. If the protein can’t bind to the gene, then it can’t keep the gene ‘turned off’ and the gene is turned back on — able to act in the way it is supposed to.”
Nelson noted that the discovery is particularly exciting because of previous research that shows the importance of being able to alter the methylation process in DNA. When mice were developed without the gene that permits this process, they don’t develop cancer. When the gene is removed from cancer cells, they “turn on” genes again in appropriate ways. “The small molecules that we’ve discovered mimic this process, so they may be very exciting lead candidates for the next generation of drugs that may help restore gene function in prostate cancer,” said Nelson.
“This entire field of exploration has been tantalizing for a decade,” said Nelson, “but has only begun to deliver fruit in just the past couple of years. This mechanism of action permits us to look for much more targeted therapies for prostate cancer, and for other cancers as well, such as breast cancer.”
The promise of this field is evident in the current pipeline of diagnostic and therapeutic products in development. There are diagnostic tests being tested that focus on detecting the methylated DNA, which would permit prostate cancer diagnosis at an earlier stage and in a more precise manner. There is also a first generation of FDA-approved medications that work to reverse the methylation process in cancer cells. They include azacitine (Vidaza) and decitabine (Dacogen), both for the treatment of myelodysplastic syndrome, diseases in which the production of blood cells by the bone marrow is disrupted. Vorinostat (Zolinza) also works to turn back on silenced genes, and is approved for use in cutaneous T cell lymphomas.
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