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Oncometabolites in cancer aggressiveness and tumour repopulation

2019; Wiley; Volume: 94; Issue: 4 Linguagem: Inglês

10.1111/brv.12513

1469-185X

Ilaria Dando, Elisa Dalla Pozza, Giulia Ambrosini, Margalida Torrens‐Mas, Giovanna Butera, Nidula Mullappilly, Raffaella Pacchiana, Marta Palmieri, Massimo Donadelli,

Histone Deacetylase Inhibitors Research

ABSTRACT Tumour repopulation is recognized as a crucial event in tumour relapse where therapy‐sensitive dying cancer cells influence the tumour microenvironment to sustain therapy‐resistant cancer cell growth. Recent studies highlight the role of the oncometabolites succinate, fumarate, and 2‐hydroxyglutarate in the aggressiveness of cancer cells and in the worsening of the patient's clinical outcome. These oncometabolites can be produced and secreted by cancer and/or surrounding cells, modifying the tumour microenvironment and sustaining an invasive neoplastic phenotype. In this review, we report recent findings concerning the role in cancer development of succinate, fumarate, and 2‐hydroxyglutarate and the regulation of their related enzymes succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase. We propose that oncometabolites are crucially involved in tumour repopulation. The study of the mechanisms underlying the relationship between oncometabolites and tumour repopulation is fundamental for identifying efficient anti‐cancer therapeutic strategies and novel serum biomarkers in order to overcome cancer relapse.