A molecular basis for this aberrant bone-mimicking behavior was identified in the finding of additional copies of key osteomimicry-associated regions of tumor cell DNA, reported Andrew J. Armstrong, MD, ScM, FACP. Dr Armstrong is an associate professor of medicine, surgery, pharmacology, and cancer biology and associate director for clinical research in genitourinary oncology at the Duke Cancer Institute.

Metastatic tumor tissue in bone more readily took up radium-223 than did surrounding normal bone tissue, he noted, suggesting that the tumor cells may be taking up calcium and therefore radium-223 directly because of this form of cellular plasticity.


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“Essentially, we have found evidence for osteomimicry in prostate cancer as a basis for explaining some of the therapeutic benefit of radium-223, a life-extending radiopharmaceutical, in men with metastatic prostate cancer,” Dr Armstrong said.

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“We found enhanced uptake of radium in cancer cells in the bone directly as compared to normal bone,” Dr Armstrong said. “Our study identified genetic and protein-based evidence of osteomimicry in CTCs and cell lines derived from CTCs from these patients over time.”

Osteomimicry involves prostate cancer cells taking on the appearance and function of bone, he explained. The finding might help explain why prostate cancer cells so frequently spread to bone tissue.

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Researchers are rethinking the current strategies for delivering radium-223 to bone metastases, said Dr Joe O’Sullivan, a professor at the School of Medicine, Dentistry and Biomedical Sciences at Queen’s University Belfast in Northern Ireland.

It remains the only molecular radiotherapeutic agent with “proven survival benefit,” though a number of other radionuclides are in development for use against tumors in non-bone environments, Dr O’Sullivan noted.

He described strategies aimed at improving the therapeutic ratio of radium-223 for treating metastatic prostate tumors in bone, including an increased number of treatment cycles (from 6 to 12), adding a second 6-cycle course of treatment, and combination with other therapies, including abiraterone, enzalutamide, docetaxel, and immunotherapeutic agents.

“We now have a greater understanding of the bone microenvironment and how prostate cancers are both attracted to, and interact with, this environment,” Dr O’Sullivan said.

Bone biology, in addition to metastatic tumor biology, is key to understanding metastasis.

“Despite the many developments in therapeutics for advanced prostate cancer, most patients who die from prostate cancer do so largely because of bone involvement: bone marrow failure [and] complications of fractures,” noted Dr O’Sullivan. “The bone is the main source of pain and immobility for these patients.”

References

  1. Armstrong AJ, Gupta S, Healy P, et al. Genomic and phenotypic evidence for prostate cancer osteomimicry in circulating tumor cells from men with metastatic castration resistant prostate cancer (mCRPC) treated with radium-223. Oral presentation at: 2018 Genitourinary Cancers Symposium; February 8-10, 2018; San Francisco, CA.