What is the role of the aryl hydrocarbon receptor (AHR) in pancreatic cancer cells, and how does its modulation affect the response to gemcitabine?

Label:chem

Topic
Pancreatic cancer (PC) is characterized by chemoresistance, particularly to gemcitabine, a commonly used chemotherapeutic agent. The aryl hydrocarbon receptor (AHR) is a transcription factor that is often upregulated in pancreatic cancer cells and has been implicated in chemoresistance through its interaction with RNA-binding protein ELAVL1 (human antigen R).
Answer
Modulation of AHR activity significantly impacts the response to gemcitabine. Inhibition of AHR activity using a selective small-molecule inhibitor (BAY) increases gemcitabine effectiveness by enhancing the expression of deoxycytidine kinase (DCK), the enzyme responsible for converting gemcitabine to its active form. Conversely, activation of AHR with an agonist (tapinarof) decreases gemcitabine effectiveness by reducing DCK expression. This suggests that AHR inhibition could be a promising strategy to improve gemcitabine treatment outcomes in pancreatic cancer.
Return to Home Chemical List
Knowledge you may be interested in
How can DHA be used in the synthesis of lactic acid? What are the potential side-reactions of DHA in aqueous solutions? How is DHA produced industrially? What is the role of DHA in glycolysis? What is the primary industrial application of dihydroxyacetone (DHA)? How does the pH of the culture medium affect the production of dihydroxyacetone (DHA)? What is dihydroxyacetone (DHA) and what are its applications? What is the role of crude glycerol in the production of dihydroxyacetone (DHA)? What is the role of hydrogen pressure in the selective conversion of furfural to cyclopentanone and cyclopentanol? How does the reaction temperature influence the conversion of furfural and the yield of cyclopentanone? How does the selective small-molecule AHR inhibitor BAY affect gemcitabine response in pancreatic cancer cells? What is the role of ELAVL1 in gemcitabine resistance, and how does AHR modulation affect its function? What is the significance of PTGS2 in the context of AHR modulation and gemcitabine response? What role does gemcitabine play in pancreatic cancer treatment? How does cytidine deaminase (CDD) affect gemcitabine efficacy? Which bacterial species are implicated in gemcitabine resistance through CDD-mediated degradation? What is the role of hydrazine hydrate in the synthesis of unprotected 3-aminoindoles? What is the significance of nitrostyrene in the synthesis of 3-aminoindoles? What are the key intermediates formed during the synthesis of 3-aminoindoles? What is the role of diethyl oxalate (DEO) in various industrial applications?