On July 1, 2026, Duke Rollie Endowed Assistant Professor of Pathology Jung Wook Park, PhD, received a $3 million, 5-year grant from the National Cancer Institute (NCI) and the National Institutes of Health (NIH) to investigate new molecular mechanisms that drive one of the most aggressive forms of prostate cancer and to identify potential therapeutic targets for future treatments.
The federally funded project builds on Park's growing body of research focused on neuroendocrine prostate cancer (NEPC), a highly aggressive subtype that develops in approximately 20–25% of patients originally diagnosed with conventional prostate adenocarcinoma. Although patients may initially respond to existing therapies, NEPC often becomes resistant to treatment and progresses rapidly, stressing the urgent need for new therapeutic approaches.
Park and his team will investigate the role of Neuronal Pentraxin 1 (NPTX1), a protein they recently identified as being selectively expressed in neuroendocrine prostate cancer but not in more common forms of prostate cancer. Previous studies from the Park Laboratory demonstrated that NPTX1 promotes tumor growth and neuroendocrine differentiation, while loss of the protein suppresses disease development in preclinical models.
"Our preliminary findings suggest that NPTX1 is a critical driver of neuroendocrine prostate cancer progression," said Park. "This grant will allow us to better understand the biological mechanisms underlying this disease and evaluate new strategies that could ultimately benefit patients with advanced, treatment-resistant prostate cancer."
The project will focus on understanding how NPTX1 interacts with histone deacetylase 6 (HDAC6), an enzyme the research team identified as a direct binding partner of NPTX1. Early studies indicate that activation of the NPTX1-HDAC6 pathway promotes cancer cell growth, neuroendocrine differentiation, and metastatic behavior. Conversely, inhibiting either NPTX1 or HDAC6 significantly reduces tumor growth in laboratory models.
In order to determine the pathway's role in disease progression, the research team will:
- Define the function of NPTX1 and its downstream regulatory genes in neuroendocrine prostate cancer
- Investigate how NPTX1 regulates HDAC6 and other molecular pathways that contribute to tumor growth and treatment resistance
- Evaluate the therapeutic potential of HDAC6-targeted therapies using human xenograft and patient-derived xenograft models
The study will use advanced animal and patient-derived models that closely replicate human disease, enabling researchers to assess how potential therapies perform in biologically relevant settings.
The new award represents a significant milestone in a broader research program aimed at understanding how prostate cancer cells adapt and become resistant to treatment. Earlier this year, Park received a Duke Cancer Institute pilot award to study mechanisms that drive lineage plasticity and tumor progression in neuroendocrine prostate cancer. More recently, he highlighted emerging therapeutic targets—including NPTX1 and HDAC6—during an invited research seminar at UT Health San Antonio.
Successful completion of the project is expected to provide new insights into the molecular events that drive neuroendocrine prostate cancer and establish whether HDAC6 inhibition could serve as a promising treatment strategy for patients with advanced disease.
"Prostate cancer remains a major public health challenge, particularly when tumors evolve to resist standard therapies," Park said. "By identifying the molecular mechanisms that enable these cancers to grow and adapt, we hope to uncover new vulnerabilities that can be translated into more effective treatments."
Learn more about the Park Laboratory and its research on prostate cancer biology and therapeutic target discovery.