Circadian Genes as Therapeutic Targets in Pancreatic Cancer

Abstract

Pancreatic cancer is one of the most lethal cancers worldwide due to its symptoms, early metastasis, and chemoresistance. Thus, the mechanisms contributing to pancreatic cancer progression require further exploration. Circadian rhythms are the daily oscillations of multiple biological processes regulated by an endogenous clock. Several evidences suggest that the circadian clock may play an important role in the cell cycle, cell proliferation and apoptosis. In addition, timing of chemotherapy or radiation treatment can influence the efficacy and toxicity treatment. Here, we revisit the studies on circadian clock as an emerging target for therapy in pancreatic cancer. We highlight those potential circadian genes regulators that are commonly affected in pancreatic cancer according to most recent reports.

Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer

“…An additional loop formed by ROR and NR1D1/2 regulates the main cycle [18,20]. In addition, a machinery of post-translational modifications is involved in the regulation of the correct ticking of the clock, including phosphorylation, acetylation/deacetylation, SUMOylation or methylation [21].…”

“…In addition, the effectiveness of treatments in various types of cancer depends on the circadian clock [23]. Therefore, the integration of circadian biology into cancer research offers new options for the prevention, diagnosis and treatment of this disease [21,24,25].…”

Exploring the metabolic landscape of pancreatic ductal adenocarcinoma cells using genome-scale metabolic modeling

“…NR1D1 positively regulates bile acid synthesis. Circadian clock regulator genes, including NR1D1 have previously been identified as therapeutic targets for cancer treatment ( García-Costela et al., 2020 ). The circadian clock is important for its role in the cell cycle, cell proliferation, and apoptosis.…”

NFIC regulates ribosomal biology and ER stress in pancreatic acinar cells and suppresses PDAC initiation

“…Exemplary genes include Cfi, Fos, genes involved in ER stress and UPR Dnajc5, Dnajc13, Hsp90aa1, circadian clock regulator Per2, and Pparg, Rara, and Rarg (Figure 3H). These pathways have been shown to be critically relevant in pancreatic homeostasis and disease 23,[27][28][29][30][31][32] .…”

“…The copyright holder for this preprint this version posted August 9, 2021. ; https://doi.org/10.1101/2021.08.09.455477 doi: bioRxiv preprint 9 regulator Per2, and Pparg, Rara, and Rarg (Figure 3H). These pathways have been shown to be critically relevant in pancreatic homeostasis and disease 23,[27][28][29][30][31][32] .…”