Breakthrough discovery could lead to development of future therapeutics for prostate cancer

Drs. Andrew Goldstein, Owen Witte, and Tanya Stoyanova and their colleagues from UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have found that prostate cancer can develop in one type of stem cell, then evolve to be maintained by a stem cell that looks very different, making prostate cancer stem cells a "moving target" for treatments. The breakthrough discovery connects directly to the development of future therapeutics that target cancer and was published online ahead of print in the Proceedings of the National Academy of Sciences.

Adult stem cells are tissue-specific regenerative cells that replace diseased or damaged cells in the body's organs. Drs. Goldstein, Witte and colleagues previously reported in Science that prostate cancer can start in basal type stem cells. Building on that discovery, they found that tumors can start in basal stem cells that evolve to luminal-like cells. This means that the source of the disease they wish to target with therapy - the tumor stem cell - can change over time.

"People have begun to think about cancers as being driven by stem cells in the same way that many of our adult organs are maintained by dedicated stem cells," said Goldstein, "based on this new understanding, a lot of excitement surrounds the concept of going right to the root of the tumor and targeting those stem cells to eradicate the cancer."

In patients with aggressive prostate cancer who are being treated with anti-androgen therapy, the basal stem cells that start the cancer look different from the luminal cells that maintain the aggressive disease, and in turn the tumor stem cells that remain after the anti-androgen treatment look different from the previous two. This means that for targeting treatments, researchers need to identify cell types that evolve as the disease and its treatment progress.

With the knowledge that prostate cancer stem cells can change what they look like, the researchers are now seeking the possible elements that are consistent within the stem cells and do not change through stem cell evolution. This knowledge will help in the development of drugs that target the evolving cancer stem cells. Drs. Stoyanova, Goldstein, Witte and their colleagues have begun to look at some of the factors that define a stem cell no matter its external appearance. They underscored the importance of the continual evolution of the stem cell's physical appearance, especially as tumors adapt to become resistant to new and more potent therapies.