Pancreatic cancer, the fourth deadliest cancer in the U.S., is very hard to detect in its early stages. Rarely diagnosed early and usually spreading rapidly, the disease has a poor prognosis. University of Houston researchers are seeking to develop drugs to enable physicians to prolong patient survival and, possibly, even eradicate pancreatic cancer, according to an article in Drug Discovery & Development
According to cancer biologist Chin-Yo Lin, an assistant professor with the UH Center for Nuclear Receptors and Cell Signaling (CNRCS), "Our research on the role of liver X receptors, or LXRs, in pancreatic cancer cells points to a promising target and strategy in the treatment of pancreatic cancer. We examined the levels of LXRs in patient tumor samples and studied the effects of candidate drug compounds targeting LXRs on cultured pancreatic cancer cells."
Lin explained that liver X receptors are key regulators of cholesterol, glucose metabolism and inflammatory response modulation. In collaboration with CNRCS director Dr. Jan-Åke Gustafsson, a pioneer in the discovery of LXRs and the Robert A. Welch Professor in Biology and Biochemistry in the UH College of Natural Sciences and Mathematics, Lin has helped to amass evidence to implicate the involvement of LXRs in numerous malignancies.
The researchers expect their ongoing studies to help determine whether LXRs are expressed in all tumors or a specific subset of tumors that could be sensitive to drugs targeting LXRs. Another objective is to determine the effects of the drugs on pancreatic tumors in mouse models that are similar to those found in humans. Eventually, they anticipate using the knowledge from these studies to develop better drugs to target LXRs in pancreatic cancer and other malignancies.
The team has done some preliminary studies of LXR expression in patient tumor samples and is preparing to investigate more samples. Recent studies demonstrated that chemical compounds targeting LXRs can retard the growth of tumors in murine models transplanted with human tumor cells.
As Lin said, "Our findings point to a class of receptors that can be precisely targeted by drug compounds and are expected to stimulate both basic and translational research on their functions and application as a drug target. Long-term goals are to develop additional drug compounds and clinical testing in human subjects, which will require several more years of research."
He concluded, "Our next steps are to collect more information from patient samples and data from pre-clinical studies. Based on the results, we will then move forward with clinical studies using existing compounds or partner with biotech or pharmaceutical companies to develop better drug candidates."