PNAS: Scientists have developed novel therapies that promise to inhibit the growth of prostate cancer in humans

Scientists from institutions such as Baylor College of Medicine have revealed the molecular mechanisms
driving the growth of advanced prostate tumors tolerant to standard castration therapy.

Androgen receptor (AR) signaling is critical to driving prostate cancer, the cancer with the highest rate of diagnosis among male cancer patients in the United States and the second leading cause of
cancer-related death.
Finding valuable therapeutic means to treat prostate cancer has always been the direction of
scientists' research.

Recently, in a study published in the international journal Proceedings of the National Academy of Sciences, entitled "A COP1-GATA2 axis suppresses AR signaling and prostate cancer", scientists from Baylor College of Medicine and other institutions have revealed the driving response to standard castration therapy through in-depth research Castration therapy) tolerates the molecular mechanisms of advanced prostate tumor growth, and after studying cells and animal models in the laboratory, researchers have discovered a new way to inhibit the growth
of therapies-tolerant tumors.

Yang said that advanced prostate cancer can usually be treated by blocking the action of androgens, a male hormone that helps prostate cancer grow, and although it is initially effective, this treatment, called castration therapy, is usually ineffective against tolerant tumors, so that tumors continue to grow and pose a fatal risk
to patients 。 By finding new ways to inhibit tumor growth in the body, the researchers studied the specific signals that tumor cells can drive cell proliferation, and they said that the activation of androgen receptors remains a key driver of castration-resistant tumor growth, so the researchers focused on a factor called GATA2, which promotes the expression and activation
of androgen receptors.

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Yang said, although it is still challenging to directly inhibit the activity of GATA2, enhancing the degradation of GATA2 to prevent the activation of androgen receptors seems to be a reasonable therapeutic strategy.
We found that the enzyme COP1 may drive the degradation of GATA2, and this process may be followed by a surprising inhibitory effect on the expression and activation of androgen receptors; Importantly, when the researchers promoted the degradation of GATA2 in animal models, tumor growth and castration therapy tolerance were significantly inhibited
.

Prostate cancer is the second leading cause of cancer death in men in the United States and the fifth largest male cancer in the world, and this study provides new ideas that may help researchers develop new and improved therapies to treat castration-resistant prostate cancer, and also supports scientists to further study this strategy into clinical applications
。 In summary, the results of this study suggest that GATA2 may be a major COP1 substrate for prostate cancer, and the promotion of GATA2 degradation by COP1 may be the direct mechanism
behind regulating androgen receptor expression and activation, prostate cancer growth and cancer tolerance to castration therapy.
(Bio Valley Bioon.
com)

Original source:

Tao Shen,Bingning Dong,Yanling Meng, et al.
A COP1-GATA2 axis suppresses AR signaling and prostate cancer, Proceedings of the National Academy of Sciences (2022).
DOI: 10.
1073/pnas.
2205350119