Researchers have discovered the mechanism by which a recently described subtype of aggressive prostate cancer spreads, even after treatment with next-generation androgen receptor (AR) inhibitors. They also report pre-clinical results in which they combine an inhibitor molecule with current immunotherapy drugs in mouse models to halt metastasis – even reversing it in some cases. The findings, which appear in the 18 July 2019 issue of Cancer Cell, offer hope for men with difficult-to-treat double-negative prostate cancer (DNPC).
“The findings open up potential new approaches to treating DNPC,” said senior author Filippo Giancotti, M.D., Ph.D., professor of cancer biology at The University of Texas M.D. Anderson Cancer Center, in a press release.
Nearly 200,000 new cases of prostate cancer are reported every year and 30,000 men die from the disease According to the Center for Disease Control and Prevention. Research has shown that prostate cancer growth is driven by the sex hormone androgen. Androgen deprivation therapy, either by castration or using androgen receptor-blocking drugs, has become the first line of therapy for this disease. But, when it spreads, physicians have found that targeted immunotherapy can work in some cases. In others, as with DNPC, Surprisingly, the cancer actually seems to respond to immunotherapy with evasive mechanisms and goes on to spread.
In the new study, researchers describe how an epigenetic regulator known as the polycomb repressor complex 1 (PRC1) coordinates the initiation of metastasis by increasing the regenerative capacity of metastatic cells. They also found that PRC1 works by suppressing the immune system and spurring tumor blood vessel growth, or angiogenesis.