Prostate cancer, which currently affects 3 million men in the United States, is no longer a death sentence if caught early. The five-year survival rate is very high (~98%) because of effective treatments like hormone therapy, chemotherapy, surgery, and radiation—and for many men with slow-progressing tumors, the wait-and-watch approach offers an alternative to treatment.
However, for those patients who have more aggressive forms of prostate cancer, where the tumors spread to other organs and tissues, the five-year survival rate is much lower (~28%), and standard therapies only work temporarily until the tumors become resistant to them. Thus, we need new therapeutic targets that lead to more effective, longer-lasting treatments.
Kinases are ABL to cause cancer
We recently wrote a blog about prostate cancer featuring the work of a pioneer in cancer research, Dr. Owen Witte from the UCLA Broad Stem Cell Research Center. Dr. Witte is well known for his work on understanding the biology of blood cancers (leukemias) and the role of cancer stem cells. One of his key discoveries was that the cancer-causing BCR-ABL gene produces an overactive protein kinase that causes chronic myelogenous leukemia (CML).
Protein kinases are enzymes that turn on key cell processes like growth, signaling, and metabolism, but they can also drive several forms of cancer. This has made some kinases a prime target for developing cancer drugs that block their cancer-causing activity.
New targets for late-stage prostate cancer
Recently, Dr. Witte’s interests have turned to understanding and finding new treatments for aggressive prostate cancers. He has been on the hunt for new targets, and this week, Witte and his group published a CIRM-funded study in the journal PNAS showing that a specific set of kinases are involved in causing advanced-stage prostate cancer that spreads to bones.
They selected 125 kinases known to be active in aggressive forms of human cancers. From this pool, they found that 20 kinases caused metastasis, or the spread of cancer cells from the original tumor to other parts of the body, when activated in mouse prostate cancer cells injected into the tail veins of mice.
To narrow the pool further, they activated each of the 20 kinases in human prostate cancer cells and injected these cells into mouse tails. They found that five kinases caused the cancer cells to leave the tail and metastasize to the bones. When they compared the activity of these five kinases in late-stage and early-stage prostate cancer cells, as well as normal prostate cells, they found activity only in late-stage cancer cells.
New treatment option?
Witte and his colleagues concluded that these five kinases can cause prostate tumor cells to spread and metastasize into bones, and that targeting kinase activity could be a new therapeutic strategy for late-stage prostate cancer patients who have exhausted normal treatment options.
In a UCLA press release, Claire Faltermeier, the study’s first author and a medical and doctoral student in Witte’s lab, commented:
Our findings show that non-mutated protein kinases can drive prostate cancer bone metastasis. Now we can investigate if therapeutic targeting of these kinases can block or inhibit the growth of prostate cancer bone metastasis.
Dr. Witte followed up by mentioning the promise of targeting kinase activity for late-stage prostate cancer:
Cancer-causing kinase activity has been successfully targeted and inhibited before. As a result, chronic myelogenous leukemia is no longer fatal for many people. I believe we can accomplish this same result with advanced stages of prostate cancer with a fundamental understanding of the cellular nature of the disease.
