Prostate cancer is a common type of cancer that occurs in the prostate gland, which is found only in males. In men with castration resistant prostate cancer, the tumors continue to grow even after surgical treatment. A new approach that suppresses the growth of therapy-resistant prostate tumors has been discovered.
“Although initially effective, this treatment, called castration therapy, often becomes ineffective as tumors develop resistance to it and are able to continue growing, a lethal condition,” said Yang, assistant professor of molecular and cellular biology and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor.
Prostate Cancer Treatment
Looking for ways to suppress these tumors’ growth, Yang and his colleagues studied signals tumor cells use to drive cell proliferation. They knew that androgen receptor activation remained a key driver of the growth of castration-resistant tumors, so they focused on GATA2, a factor known to promote androgen receptor expression and activation.
“While directly inhibiting GATA2 activity remains challenging, enhancing GATA2 degradation to prevent androgen receptor activation seemed a plausible therapeutic strategy,” Yang said. “We discovered that the enzyme COP1 drives GATA2 degradation, and that this was followed by striking inhibition of androgen receptor expression and activation. Importantly, when we promoted GATA2 degradation in our animal models, tumor growth as well as castration resistance were markedly suppressed.”
Tao Shen, Bingning Dong and Yanling Meng at Baylor College of Medicine and David D. Moore now at University of California, Berkeley, also contributed to this work.
This research was supported by grants from the Department of Defense Congressionally Directed Medical Research Programs (W81XWH17-1-0043), the Cancer Prevention Research Institute of Texas (RP130651) and the R.P. Doherty Jr.-Welch Chair in Science (Q-0022).
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