Research uses circadian rhythm to attack pancreatic cancer
Recent research from the lab of Faraz Bishehsari, MD, PhD, professor in the Department of Internal Medicine and director of the Gastroenterology Research Center, showing that pancreatic cancer cells follow daily circadian rhythm cycles has been published in JCI Insight under “Circadian transcriptome of pancreatic adenocarcinoma unravels chronotherapeutic targets.
Circadian rhythm is the daily routine of functions and behaviors that have developed over in response to environmental changes for most species, including humans. These rhythms are present in not only healthy cells, but also cancer cells in tumors as well.
“I believe that because the molecular patterns of tumors can vary between individuals, there are also differences in tumor rhythms, which can affect how well treatment works for each person,” Bishehsari said. “Our study suggests that pancreatic cancer has daily rhythms in gene activity, which could help find new drug targets to improve personalized timing of treatments for this cancer.”
The lab’s research focused on pancreatic ductal adenocarcinoma (PDA), a deadly form of cancer with a 5-year survival rate of just 4.2% according to a 2020 study published in Nature. PDA cannot be treated with surgery, leaving ineffective and limited options for treatment for a disease with a growing incidence rate.
Using samples taken from the pancreas, the lab created miniaturized and personalized pancreatic cancer cells called organoids. The researcher then studied the organoids to see how their gene activity changes while also using well-known human cancer cell lines to study circadian rhythms and test their response to drug therapies.
“For the first time, we observed that there is a daily rhythm in gene activity of the personalized pancreatic cancer cells that vary from one organoid to another,” Bishehsari said. “We confirmed that some of these time-dependent variations were mostly unique to cancer.”
While continuing to look at the changes in the cells, the lab was able to identify pathways of possible treatments that could be tied to the rhythms of the organoids and were also able to test the effectiveness of some of top drug candidates available to verify the lab’s findings.
Moving forward, the lab will continue studying the daily rhythms of both cells and patient samples, in order to further understand new patterns and help build detailed models of potential targets for time-based cancer treatments. Additionally, they hope to look at the mechanisms that cause the rhythmic patterns in cancer cells.
“This study shows that our approach could be used to create personalized, time-based treatments for pancreatic cancer, based on the unique patterns of each person’s tumor,” Bishehsari said. “We hope in the future we can say not only what drug, but also what time it could work best in a certain tumor.”