Lethal Metastatic Prostate Cancer May Spread from Other Sites

What You Need to Know: Multiple targeted therapies may be needed to combat metastatic prostate cancer because metastasis may be spread from multiple tumor clones according to a new study. “{The findings} are eye-opening,” said study investigator William Isaacs, PhD, who is a professor of urology at the Johns Hopkins Brady Urological Institute and a member of The Johns Hopkins Kimmel Cancer Center in Baltimore, MD. “It emphasizes the aspects that these cancers are evolving at an almost continual rate.”

The Study: Using whole-genome sequencing, Dr. Isaacs and colleagues characterized multiple metastases arising from prostate tumors in 10 men with metastatic castration-resistant prostate cancer (mCRPC). The team analyzed the subclonal architecture of prostate cancer cells and found that:

  •  Metastasis-to-metastasis spread was found to be common through de novo monoclonal seeding of daughter metastases.
  • Researchers found a transfer of multiple tumor clones between metastatic sites in 5 of the 10 patients.

The researchers believe that a new view of mCRPC is now emerging that tumor cells share a common heritage but subclones develop metastatic potential. The data suggest clonal diversification may occur in part as a necessity to bypass androgen deprivation therapy (ADT) and subsequently drive distinct subclones onto a convergent path of therapeutic resistance.

My Take: Whole-genome sequencing on the samples showed that even though a single cell begins the metastatic process, the disease becomes very heterogeneous as it spreads throughout the body over time. These new findings support the notion that treatments for metastatic cancers should include a combination of therapies that target a variety of genetic pathways.  The idea that metastatic tumors can seed and establish other metastatic tumors in patients is different from traditional theories that the primary tumor is solely responsible for disseminating cancer cells with metastatic potential. To me, this work is beautiful, pointing to a new way to see and manage metastatic cancer. I’m Dr. Michael Hunter.

Reference: Gundem G, Van Loo P, Kremeyer B, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520(7547):353-357.

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Harvard AB Yale MD UPenn Radiation Oncology Radiation Oncologist, Seattle area

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