NIH Reporter #1R03OD039982-01

Discovery of Chronotherapeutic Candidate Targets in Pancreatic Cancer

This award funds research to identify time-dependent treatment targets in pancreatic cancer by analyzing circadian rhythms in tumor gene expression and leveraging multiple datasets to find druggable chronotherapeutic targets.

Description

Our "clock" system regulates diurnal variations (circadian rhythms) in biological processes to synchronize with Earth's 24-hour rotation. This rhythmic pattern presents opportunities for time-dependent treatments of diseases, including cancer, known as chronotherapy. Recent data from our group and others indicates that tumors exhibit temporal gene expression, with variability in rhythmic patterns among individual tumors. Mapping tumor-specific circadian rhythms is crucial to advancing chronotherapy towards clinical application, despite logistical challenges in human organ sampling. We propose to analyze Common Fund program datasets to develop a framework for targeting chronotherapeutic processes against cancer, focusing on pancreatic ductal adenocarcinoma (PDA). Aim 1 involves profiling the cancer-specific molecular rhythmicity of human pancreatic tissue, including tumor and tumor-infiltrating immune cells, utilizing resources such as GTEx, GEO, TCGA, and COSMIC. Aim 2 aims to identify potential druggable targets for chronotherapy in PDA, leveraging datasets from KOMP2, LINCS, IDG, and Drug Bank. These studies will demonstrate a proof-of-concept for expanding dataset use in identifying chronotherapeutic targets.

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