Pancreatic cancer is one of the most aggressive forms of cancer and often spreads to other parts of the body. African American communities experience especially high rates of pancreatic cancer and death from the disease. Although treatments have improved, commonly used chemotherapy drugs such as gemcitabine and fluorouracil (5-FU) often have limited effectiveness because tumors can become resistant to them. These treatments can also cause serious side effects that limit the amount patients can safely receive.
Our research team has developed two experimental compounds, SYA013 and SYA014, from haloperidol, an approved medication that has also shown an ability to slow the growth of cancer cells. In previous laboratory studies, these compounds killed several types of cancer cells, including pancreatic cancer cells, while causing less harm to noncancerous cells. They also showed promising results when combined with paclitaxel, another chemotherapy drug, in laboratory and animal models of triple-negative breast cancer.
In this project, we will study whether SYA013 and SYA014 could improve pancreatic cancer treatment. We will test the compounds in several pancreatic cancer models, including cancers that are resistant to multiple drugs, and compare their effects on cancerous and healthy pancreatic cells. We will also combine SYA013 or SYA014 with gemcitabine or 5-FU to determine whether the drugs work better together than they do alone. The most promising combinations will then be tested in three-dimensional tumor models grown from patient tissue.
The research team will examine how these treatments affect cancer cell growth, survival, movement, and ability to spread. We will also investigate how the drug combinations work and why they may be more effective together. Finally, the most successful treatment combination will be tested in mice carrying pancreatic tumors derived from an African American patient. Tumor samples will be studied to determine how the treatment causes cancer cells to die.
Our goal is to develop a more effective pancreatic cancer treatment that reduces drug resistance and limits harmful side effects. This work supports the National Institutes of Health’s goal of reducing health disparities and improving health outcomes across all populations.
The project brings together experts in drug development, cancer biology, tumor genetics, preclinical testing, and pancreatic disease. Dr. Chandra Voshavar specializes in developing small-molecule treatments for cancer and disorders of the central nervous system. Dr. Salhia has extensive experience studying tumor biology and testing treatments in patient-derived tumor models. Dr. Assarzadegan is a pathologist with specialized expertise in diseases of the gastrointestinal system, liver, and pancreas. Together, the team aims to advance a promising new treatment strategy for pancreatic cancer
If you share our interest in reducing cancer health disparities, please consider becoming a member of the CaRE² center. Investigators, trainees, community leaders, and advocates are welcome.