Che-Chia Hsu, PhD, assistant professor of pathology at Duke University School of Medicine, has received a Duke Cancer Institute (DCI) American Cancer Society (ACS) Institutional Research Grant Pilot Award for his project, "Targeting IMPA1/Inositol to Overcome Immunotherapy Resistance in Castration-Resistant Prostate Cancer." The one-year award supports promising early-career investigators conducting innovative cancer research.
The project will explore new ways to help the immune system recognize and attack advanced prostate cancers that no longer respond to standard hormone-based treatments. Known as metastatic castration-resistant prostate cancer (mCRPC), this aggressive form of the disease remains difficult to treat, and current immunotherapies have had limited success in many patients.
Hsu's research aims to uncover why these tumors are often able to evade the body's immune defenses. Specifically, his team is studying IMPA1, an enzyme involved in producing inositol, a naturally occurring molecule that helps regulate cell signaling and growth. Previous studies from Hsu's laboratory found that IMPA1 is highly active in prostate cancer stem cells and may help drive treatment resistance and tumor progression.
"We believe some prostate cancers may be able to alter their metabolism in ways that allow them to hide from the immune system," said Hsu. "By understanding how this process works, we hope to identify new strategies that make these tumors more visible to immune cells and more responsive to immunotherapy."
The project will investigate how IMPA1-derived inositol affects the ability of cancer cells to display warning signals, known as antigens, on their surface. These antigens help the immune system recognize abnormal cells. When that process breaks down, tumors can become "invisible" to immune attack.
Hsu and colleagues will also evaluate whether combining drugs that target IMPA1, or its related regulatory protein, with existing immunotherapy approaches can improve treatment responses. Their long-term goal is to transform so-called "cold" tumors that attract few immune cells into "hot" tumors that are more likely to respond to immunotherapy.
The project may ultimately lead to new biomarkers for predicting treatment response and lay the groundwork for combination therapies for patients with advanced prostate cancer.
Hsu emphasized that the award was made possible through the support and mentorship of senior Duke Pathology leaders. The study includes Jiaoti Huang, MD, PhD, Johnston-West Endowed Chair of Pathology, and Hui-Kuan “Kevin” Lin, PhD, professor of pathology and director of Prostate Cancer Research, as key personnel.
"This project would not have been possible without the support of Dr. Huang and Dr. Lin," Hsu said. "Their guidance, expertise, and commitment to advancing prostate cancer research have been invaluable."
"Dr. Hsu is pursuing an innovative line of investigation that bridges cancer metabolism and tumor immunology," said Huang. "This work has the potential to uncover new therapeutic opportunities for patients with advanced prostate cancer."
The DCI-ACS Institutional Research Grant Pilot Award supports junior faculty conducting cancer-related research and is intended to generate preliminary data for future externally funded studies. Awards are made through a competitive peer-review process and emphasize innovation, scientific merit, and potential impact on cancer research.