Proteins may lead to prostate cancer recurrence

New research has shown that androgen-synthesizing proteins are present within cancer cells, which suggests that cancer cells may develop the capacity to produce their own androgens. The presence of these proteins 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, researchers say.

The study, funded by the Prostate Cancer Foundation and the National Cancer Institute, was presented at the foundation’s annual scientific retreat.

Peter Nelson, MD, Elahe Mostaghel, MD, PhD, and Bruce Montgomery, MD, of the Fred Hutchinson Cancer Research Center and University of Washington, conducted tests on preserved tumors removed from deceased prostate cancer patients during rapid autopsies immediately after death. All the patients had received androgen-blocking therapies during the course of treatment to suppress tumor growth.

The team was able to detect in the tumors the key proteins 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,” Dr. Nelson said. “While this study does not prove that the cancer cells act in this way, it does show it is possible.”

In the study, researchers removed entire metastases 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 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,” Dr. Nelson said.