PNAS: a new strategy to inhibit the growth of prostate cancer

The search for valuable interventions for prostate cancer treatment has guided research in Dr.
Yang Feng's lab at
Baylor College of Medicine.
In a study published in the Proceedings of the National Academy of Sciences, Yang's team took a closer look at what drives the growth
of advanced tumors that are resistant to standard castration therapies.
Through studies of laboratory cells and animal models, they discovered a way to
inhibit the growth of treatment-resistant tumors.

"Advanced prostate cancer is usually treated by blocking the action of androgens, a male hormone that helps the prostate grow," said Dan M.
M.
, assistant professor of molecular and cell biology and Baylor University of Baylor.
Yang, a member of L.
Duncan Comprehensive Cancer Center, said
.
"Although this treatment, known as castration therapy, works initially, as the tumor becomes resistant to it and is able to continue to grow, the condition tends to become ineffective, which is a fatal condition
.
"

To find ways to inhibit the growth of these tumors, Yang and his colleagues studied the signals
that tumor cells drive cell proliferation.
They knew that activation of androgen receptors remained a key driver of anti-castration tumor growth, so they focused on GATA2, a known factor
that promotes androgen receptor expression and activation.

"While direct inhibition of GATA2 activity remains challenging, preventing androgen receptor activation by enhancing GATA2 degradation appears to be a viable therapeutic strategy
," Yang said.
"We found that the COP1 enzyme drives GATA2 degradation, followed by significant inhibition
of androgen receptor expression and activation.
Importantly, when we promoted GATA2 degradation in animal models, both tumor growth and castration resistance were significantly inhibited
.
”

"Prostate cancer is the second leading cause of death for male cancer patients in the United States and the fifth leading cause of death for male cancer patients worldwide," Yang said
.
"Our study opens up a new avenue that may improve treatments for castrated prostate cancer, supporting further research to translate this strategy into the clinic
.
"

Shen Tao, Dong Bingning, and Yan Ling of Baylor College of Medicine and David D.
Moore of the current University of California, Berkeley, also contributed
to the work.