Oncometabolites in cancer aggressiveness and tumour repopulation

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.

1H-NMR Based Serum Metabolomics Identifies Different Profile between Sarcopenia and Cancer Cachexia in Ageing Walker 256 Tumour-Bearing Rats

“…Since fumarate is a key molecule in the tricarboxylic cycle, especially in neoplastic cells, it is considered one of the oncometabolites, because is found in high concentrations in cancer and adjacent cells, suggesting that this metabolite could be decreased in the serum. This condition modifies the tumour microenvironment, sustaining the invasive neoplastic phenotype [31]. The role of fumarate as an oncometabolite could explain why this metabolite is the only one altered in Wa group, reinforcing the fact of higher metastatic process found in these animals (data not shown) and verified previously [13,14].…”

Oncometabolites: A new insight for oncology

“…In the near future, the noninvasive biomarkers like oncometabolites can help the oncologist to make decisions more precisely in shorter time, especially in predicting more aggressive tumor behavior (Dando et al, ). Over the last two years, huge number of research is published in which the role of oncometabolite is highlighted not only in cancer diagnosis but also in cancer management and prognosis (Ganapathy, ; Hanover, Chen, & Bond, ; Park et al, ).…”

2-Hydroxyglutarate in Cancer Cells

“…A small molecule, such as 2HG, influences enzymes requiring 2OG as a substrate or co-factor. Since a class of such enzymes regulates epigenetics, the 2HG dysregulation of epigenetics is the ultimate mechanism of accelerated cancerogenesis (20,29,34,35,37,54,98,164), besides activation of mTOR pathway (Figs. 4 and 5).…”