Aryl hydrocarbon receptor (AHR) signalling: A double-edged sword guiding both cancer progression and cancer therapy

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 6; p. 130805
• Main Authors: Sahoo, Rahul, Pattnaik, Sriya, Mohanty, Biswajit, Mir, Showkat Ahmad, Behera, Birendra
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2025
• Subjects: AHR; AHR ligand; Animals; Aryl hydrocarbon receptor; aryl hydrocarbon receptors; Cancer; cancer therapy; carcinogenicity; Cell signalling; Disease Progression; genomics; Humans; Ligands; metastasis; neoplasm progression; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Signal Transduction; Targeted cancer therapy; Cell signalling; RB1; RELA & RELB; HIF-1α; AHR; JAK/STAT; EGFR; NF-κB; AHR ligand; NRF2; PI3K; EP300; Targeted cancer therapy; NCOA2/3; HSP90; XAP2; IL; PRMT4; ARNT; PKC; MAPK; ESR1; Aryl hydrocarbon receptor; IDO/TPH; MAF; ARE; ROS; E2f1; HRE; Cancer
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130805

Aryl Hydrocarbon Receptor (AHR) reported to be associated with major carcinogenic signalling cascades which cause cell proliferations, metastasis and invasion as well as immune imbalance. AHR Participates in cellular processes not only through genomic pathways to cause genomic alterations but also via nongenomic pathways to alter various cytoplasmic proteins. In addition, AHR senses a wide range of ligands that modulate its downstream mechanisms that are intricated in cancer induction and prevention. Thus, AHR functions as a two-sided sword where some AHR ligands contribute to enhance cancer whereas few are useful for cancer treatment. Therefore, AHR represent as a regulatory point in cancer progression and treatment. There is a need to reinvestigate the regulatory role of AHR in major intracellular pathways and to explore the potential of AHR ligand for the design of cancer therapeutics. This review emphasizes the interaction of AHR with pro-carcinogenic signalling pathways that modulate cancer induction and progression. Furthermore, it also discusses about the current discovery of AHR ligands for cancer initiation or inhibition. This information could be useful for development of therapeutic strategies for the management of cancer by targeting AHR. [Display omitted] •AHR, a cytosolic transcription factor intricated in major pro-carcinogenic pathways.•AHR creates a tumour microenvironment that promotes cancer and helps in immune escape.•AHR can be potential target for the treatment of cancer.•AHR ligands represents a novel class of anticancer compounds that requires more scientific investigation.