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Study Explains How Prostate Cancer Turns Lethal and Offers Therapeutic Solution
Last reviewed: 27.07.2025
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A major breakthrough in prostate cancer research: A first-of-its-kind study by Emory University researchers has revealed how the disease evolves into its most deadly form and identified a promising treatment strategy.
The findings, published in the journal Nature Genetics, provide key insights into why some forms of prostate cancer become resistant to therapy and how this transition can be stopped.
Transformation into an aggressive form
Researchers at Emory University have described a new step-by-step pathway by which prostate cancer cells transform into a more aggressive form known as neuroendocrine prostate cancer (NEPC). This transformation occurs in about 20% of advanced cases and leads to rapid disease progression, with no effective treatments currently available for NEPC.
"Prostate cancer is one of the most frequently diagnosed cancers, affecting a huge number of patients and their families," said lead author Jindan Yu, MD, PhD, professor of urology at Emory University School of Medicine.
"Although it responds well to hormonal therapy in the early stages, many patients develop resistance over time. One of the main pathways leading to treatment failure and disease progression is the transformation of tumor cells into NEPC, a new form of tumor that does not contain targets for existing prostate cancer drugs."
3D map of cellular transformation
Using advanced genomic technologies and in collaboration with Dr. Jonathan Zhao, associate professor of human genetics, the team created the first 3D map of how prostate cancer cells are reprogrammed over time to become a new, more dangerous threat.
This map shows how DNA inside the cell's nucleus bends and forms loops - changes that activate genes that promote deadly transformation.
The researchers found that two proteins, FOXA2 and NKX2-1, play a central role in this process:
- FOXA2 acts as a "pioneer factor", opening up previously inaccessible regions of DNA;
- This allows NKX2-1, a gene normally active in brain and lung cells, to switch on a new genetic program that rewires the cell to become an NEPC type.
"Together, these proteins change the cell's personality and promote its transition to a more lethal form," explains Yu.
New Therapeutic Target: CBP/p300
It was also found that the enzymes CBP and p300 are necessary for the activation of a new oncogene program. These enzymes act as epigenetic switches that turn on genes that cause aggressive tumor growth.
Importantly, the researchers showed that CBP/p300-inhibiting drugs, such as CCS1477 (in clinical trials), effectively suppress the growth of NEPC tumors in laboratory and animal models.
Significance for patients
This study has significant implications for patients, their families and the future of prostate cancer treatment.
By identifying the molecular mechanisms behind NEPC transformation and showing how they can be blocked, scientists are opening the way to new treatments that could radically improve the prognosis for patients with this aggressive form of the disease.