CCRI gains nearly $2.6M from NCI for metastasis research
University of Mississippi Medical Center's research to study the mechanisms of prostate cancer bone metastasis and evaluate new therapies has gained nearly $2.6 million in funding from the National Cancer Institute.
The five-year study is focused on understanding how prostate cancer cells spread to bones and why the disease is so difficult to treat following bone metastasis, said Dr. Jawed Siddiqui, associate professor in the Department of Cell and Molecular Biology and principal investigator of the study, “The Significance of Lipoylation in Prostate Cancer Bone Metastasis to Develop Innovative Therapeutics,” at the UMMC Cancer Center and Research Institute.
"This project primarily centers on investigating the role of protein lipoylation and mitochondrial metabolism in guiding prostate cancer cells to the bone microenvironment,” Siddiqui said. “We will also investigate the importance of cuproptosis, a recently discovered form of cell death closely tied to cellular metabolic fate. We believe that prostate cancer cells hijack these metabolic processes to survive and grow in the bone.”
"This award reflects the growing strength of our cancer research enterprise and our commitment to fostering innovative science that bridges fundamental discoveries and clinical impact,” said Dr. Ajay Singh, associate director of basic and translational research at CCRI. “By investigating an emerging mechanism underlying prostate cancer bone metastasis, Dr. Siddiqui's research has the potential to identify new therapeutic strategies for one of the deadliest stages of the disease."
Lipoylation is a process cells use to “switch on” certain proteins so they can make energy. Cuproptosis occurs when excess copper accumulates in a cell, shutting down the energy-producing system. Some cancer cells are especially sensitive to this, which is why researchers are exploring whether this weakness could be exploited as a new therapeutic vulnerability.
"Understanding how cancer cells exploit lipoylation and evade cuproptosis to survive and spread may reveal vulnerabilities that extend well beyond prostate cancer, potentially informing the development of innovative therapies for a wide range of aggressive cancers," Singh said.
Siddiqui agreed. “If we can show that targeting protein lipoylation and cuproptosis can slow or prevent bone metastasis, it could lead to a completely new way of treating advanced prostate cancer and, potentially, other cancers that spread to bone. In the long term, we hope these discoveries will open new avenues for targeted therapies in precision oncology, which ultimately help patients live longer, healthier lives.”
Over the next five years, the CCRI research team will not only understand the disease mechanisms but also explore potential therapies, said Siddiqui, noting that the study is in the preclinical stage. “The vision of my lab is to generate breakthrough findings that can be translated into clinical settings.”
More than 84% of people with metastatic prostate cancer develop tumors that spread to the bone, a condition known as bone metastasis.
“Bone metastasis has a tremendous impact on patients,” Siddiqui said. “It can cause severe pain, fractures, loss of mobility and greatly reduce quality of life. Seeing the research gap between the remarkable progress made in the treatment of primary prostate cancer and the very few treatment options that exist for patients with metastatic prostate cancer has been a major motivation for my research.”
Understanding the bone metastasis of different cancers is a major focus of Siddiqui’s lab.
“The biology of bone metastasis signifies one of the most multifaceted and fascinating processes in several malignancies,” he said.
Prostate, breast, lung and kidney cancers have traits that make them more likely to spread to bone, while other cancers, such as cancers of the brain, skin or digestive system, are less likely to metastasize there.
“Our lab has long been interested in exploring the cellular pathways involved in bone metastasis of prostate, breast and lung cancers,” Siddiqui said. “Like other particular projects in the lab, this project also addresses the puzzle of why the bone is a favorable site for growth and survival of some cancer cell types.”
“We are using experimental models and innovative techniques to decipher the process and mechanisms of bone metastasis,” Siddiqui said.
Other studies underway in Siddiqui’s lab at CCRI include research into the molecular mechanism of bone metastasis, bone microenvironment, osteoimmunology, tumor dormancy, osteoimmunology and development of bone metastasis therapies.
The grant funding is paving the way for discoveries in cancer research beyond the prostate.
“Rather than this being a stand-alone study, the outcomes of this project will also shed light on the link between lipoylation and cuproptosis in relation to other cancers,” Siddiqui said. “It’s an exciting new direction that complements our ongoing work and could open the door to new treatments for metastatic disease.”