Circadian Disruption in Pancreatic Cancer
Abstract
Pancreas cancer is the Fiscal Year 2019 Peer Reviewed Cancer Research Program Topic Area addressed in this proposal. Pancreas cancer is among the deadliest of cancers, with a very poor survival rate, owing to its early spread and limited treatment options. Understanding the causes of pancreas cancer, or what leads to its rapid growth, could lead to new preventive strategies or therapies. One potential link to cancer development is disruption of a person’s circadian rhythm. Circadian rhythms are normal biologic processes that arise from environmental input, such as timing of light/dark exposure (i.e., sleep-wake cycle), and fluctuate throughout a 24-hour period. Circadian rhythms have evolved over time in humans to coordinate cell and organ function with the anticipated timing of activity and food intake (wake or light), and rest (sleep or dark). These rhythms control processes such as cell growth, metabolism, and immune function, and abnormal functioning of these rhythms due to irregular sleep patterns (circadian disruption) can cause significant pathology. Notably, circadian rhythm disruption heightens risk of immune dysfunction, obesity, and diabetes, each of which are risk factors for pancreas cancer development. However, circadian rhythm disruption has not been effectively evaluated as a link to pancreas cancer. The rationale for this proposal is that because circadian rhythm disruption affects a substantial proportion of the United States population, and because pancreas cancer is so poorly understood with limited therapies, it is imperative that the potential link between circadian rhythm disruption and pancreas cancer be investigated. The scientific objective of this proposal is to understand the extent to which circadian rhythm disruption contributes to pancreas cancer formation and spread. Achieving this objective can ultimately contribute significantly to improved patient care and outcomes for patients with pancreas cancer (and possibly translate to patients with other types of cancer). For instance, this research can contribute to improved understanding of environmental risk factors for developing pancreas cancer. Similar to behavior modification for other known risk factors (e.g., smoking cessation for cigarette smokers), interventions focusing on reinstating normal circadian rhythms can occur in order to help prevent pancreas cancer. Behavioral adjustments may include ensuring consistent sleep wake cycles when possible and an emphasis on identifying barriers to regular sleep patterns. This would be a profound shift from current thoughts on risk factors for pancreas cancer development and would be highly applicable to military personnel, Veterans, and the civilian population in general. Furthermore, this research may lead to a better understanding of what drives the rapid growth and spread of pancreas cancer once it has formed. Most people with pancreas cancer are diagnosed when the cancer is already widespread, and current therapies are minimally effective at extending life beyond 1 year after diagnosis. Thus, any contribution to improved understanding of why the cancer progresses so rapidly could lead to new ways to treat this devastating cancer. Importantly, there are already small molecule compounds (drugs) that can target abnormally functioning circadian rhythm proteins; therefore, this research could lead to a swift clinical application of novel therapy for pancreas cancer (i.e., new drugs do not have to be developed). Furthermore, establishing a link between circadian disruption and pancreas cancer could translate to a better understanding of risk factors and therapy for other cancers and would help propel understanding of how alteration of normal circadian biology can contribute to disease states. While the goal of this 2-year proposal is to understand the extent to which circadian disruption contributes to pancreas cancer formation and spread, future studies will focus on how this occurs and what n
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010612
Entities
People
- Sean Ronnekleiv-kelly
Organizations
- United States Army
- University of Wisconsin–Madison