2026, Number 2
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Rev Biomed 2026; 37 (2)
Role of tryptophan metabolism and the AHR on breast cancer
Limón-Pacheco JH, Elizondo-Azuela G
Language: Spanish
References: 34
Page: 76-83
PDF size: 264.67 Kb.
ABSTRACT
Breast cancer (BC) is one of the most common malignancies among
women worldwide. In BC, cells increase their metabolism by regulating
multiple metabolic pathways. In this descriptive review, recent literature
indexed in PubMed was reviewed, and the current state of knowledge
on tryptophan (Trp) metabolism, the kynurenine (Kyn) pathway
and its derived metabolites, their relationship with aryl hydrocarbon
receptor (AHR)-mediated signaling in BC, and their potential as a
therapeutic target was discussed. Three Trp catabolism enzymes are
overexpressed in breast cancer: indolamine-2,3-dioxygenase 1 and 2
(IDO1/2) and tryptophan-2,3-dioxygenase 2 (TDO2). They catalyze
the degradation step from Trp to Kyn an AHR ligand. The AHR is a
transcription factor characterized by its role in mediating toxicity and
adaptive responses to polycyclic aromatic hydrocarbons and has been
detected overexpressed in breast tumors. Kyn and other metabolites
derived from Trp activate signaling pathways through the AHR, which
stimulates IDO1 expression, increasing Kyn levels and promoting an
immunosuppressive circuit. Furthermore, substantial evidence has
shown that this mechanism drives the progression of BC. The idea of
inhibiting these molecules has aroused great expectations to find new
drugs for BC therapy.
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