Research done through a grant by the Prostate Cancer Foundation was presented at their recent meeting relating to the biology of advanced prostate cancer and reported in Medical Research News.
The researchers were able to detect in the tumors the key proteins, or enzymes, needed for a cell to produce its own testosterone from cholesterol present in the cell. “This study, along with other research in the field, suggests that cancer cells may have the ability to adapt and produce their own androgens that permit these cancer cells to survive,” explained Nelson. “While this study does not prove that the cancer cells act in this way, it does show it is possible.”
……. which demonstrated that testosterone and potent metabolites could still be found in prostate tumors at levels exceeding those found in the blood, which suggested the cancer could develop its own testosterone. ……. “In other studies, men without prostate cancer who received androgen-suppressing drugs also showed surprisingly high levels of androgen in their prostates even with low levels in their blood,….and biopsies of the prostate following testosterone suppression in men who have prostate cancer have shown similar results.”
The research by the Hutchinson Center/University of Washington team now offers a plausible explanation and mechanism of action for these findings. In the study, researchers removed entire metastases, or tumors, from deceased prostate cancer patients who had agreed to be part of a “rapid autopsy” research program. At least three tumors were removed from each patient, and examined for androgen levels and the presence of the enzymes responsible for androgen metabolism.
……the study offers directions for future research in this area. “The next phase will be to determine the source of androgen precursors. These are likely to be derived from andrenal androgens, or possibly from cholesterol. A key experiment will be to follow these precursor molecules in the cancer cells to see if they are converted to testosterone,…….hence proving these tumor cells are actually capable of such a conversion.”
New medications are being tested in the early stages of clinical trials with the goals of blocking androgen synthesis. Abiraterone, for example, seeks to inhibit the enzymes in the metabolic pathways that convert cholesterol to androgens, and work by blocking androgen synthesis in both the adrenal gland and possibly in the tumors themselves. Other classes of drugs being tested attempt to more completely block interactions with the receptor for androgens within the tumor cells, or alter the degradation of androgens. Rather than continuous treatment which is associated with side-effects, a strategy of maximally inhibiting the androgen axis for a short-time or on an intermittent basis could have the effect of destroying or suppressing cancer cell growth for long time periods.
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