Researchers have found that overexpression of a specific pair of genes might provide not only early warning of which prostate cancer patients are likely to progress to metastatic disease, but also therapeutic targets for halting that progression in certain patients.
When expressed concurrently in primary human prostate cancers, the genes TOP2A and EZH2 identified patients who had a faster time to biochemical recurrence and were more susceptible to metastatic disease progression, investigators wrote online in Clinical Cancer Research (Sept. 12, 2017).
Once a susceptible patient subset is identified, it may be feasible to intervene and apply an adjuvant or neoadjuvant targeted therapeutic approach to inhibit progression to metastasis, related experimental results suggest.
In a prostate cancer mouse cell line model, increased TOP2A and EZH2 resulted in hypersensitivity to treatment with etoposide, which targets TOP2, combined with an EZH2-inhibiting compound, the investigators reported.
The findings suggest concurrent overexpression of TOP2A and EZH2 is essentially “an identifier of aggressive prostate cancer,” said researcher Leigh Ellis, PhD, of Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston.
“As in most solid tumors, metastasis is what kills the patient,” Dr. Ellis said in an interview with Urology Times. “So if we can identify those patients that are going to metastasize before they do metastasize, then hopefully we can therapeutically intercept that, and the patient doesn't have to worry about that being an issue.”