Oncologists have for some time been puzzled as to why some prostate cancers recur after the use of therapies designed to stop the production of testosterone and other androgens that "fuel" tumor growth. Now, researchers from the Fred Hutchinson Cancer Research Center say that prostate cancer cells may develop the capacity to produce their own androgens (male hormones) to fuel their growth. The new discovery, presented at the Prostate Cancer Foundation annual scientific retreat, may explain why some prostate cancers become resistant to widely-used therapies, and offers new directions for research into future treatments that could block the development of androgens in the cancer cells.
Androgen-deprivation (testosterone lowering) therapy is routinely used in the treatment of advanced prostate cancer, in order to deprive cancer cells of the hormones that fuel their growth. However, the researchers say that over time, cancer cells can become "androgen independent," and grow even in the presence of these medications. This type of the cancer is a lethal form of the disease, with most patients dying 18 to 24 months after becoming resistant to hormone suppression.
Researchers Peter Nelson, Elahe Mostaghel and Bruce Montgomery conducted tests on tumors removed and preserved from deceased prostate cancer patients immediately after death. All the patients had received androgen-blocking therapies during the course of treatment to suppress tumor growth. 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."
Recent research by others supports the new finding. "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," noted Nelson, "and biopsies of the prostate following testosterone suppression in men who have prostate cancer have shown similar results."
Nelson said the study offers directions for future research. "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," said Nelson, "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.
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Source: Prostate Cancer Foundation
