Exploiting Metabolic Vulnerabilities of Cancer with Precision and Accuracy

Abstract

Links between oncogenic drivers and cancer cell metabolism have emerged over the past several decades, indicating that constitutive oncogenic growth signaling can render cancers susceptible to metabolic interventions. While significant progress has been achieved in the identification of metabolic vulnerabilities of cancer cells, the complexity of the tumor microenvironment (TME) and the dynamic nature of organismal circadian metabolism challenge the precision of targeting cancer metabolism. Here current progress in the areas of cancer metabolism and TME metabolism is reviewed, highlighting how cancer metabolism can be accurately and precisely targeted.

Multifaceted Aspects of Metabolic Plasticity in Human Cholangiocarcinoma: An Overview of Current Perspectives

“…In this scenario, the concept of tumor metabolism is worth particular interest for several reasons: (i) metabolic modification is a well-known hallmark of cancer, (ii) oncogenes drive alterations in cancer metabolism, (iii) metabolites can control gene and protein expressions, and (iv) metabolic proteins and/or metabolites represent diagnostic and prognostic biomarkers [21][22][23][24][25]. Indeed tumour cells have unique metabolic and bioenergetic features, allowing them to survive in poor nutrient environments and maximize cell growth [22].…”

The catalytic activity of serine hydroxymethyltransferase is essential for de novo nuclear dTMP synthesis in lung cancer cells

“…Tumour cells recycle one-carbon units from different amino acids within the folate and methionine cycles to produce the building blocks needed to sustain high proliferation rates [1][2][3]. Tumour cells recycle one-carbon units from different amino acids within the folate and methionine cycles to produce the building blocks needed to sustain high proliferation rates [1][2][3].…”

“…Alteration of the one-carbon metabolism (OCM) is a recognized hallmark of cancer. Tumour cells recycle one-carbon units from different amino acids within the folate and methionine cycles to produce the building blocks needed to sustain high proliferation rates [1][2][3]. The uptake of serine, the major source of one-carbon units, is coupled to a hijacking of glycolysis intermediates towards the serine synthesis pathway (SSP).…”

Mitochondria-centric bioenergetic characteristics in cancer stem-like cells

“…From a metabolic perspective, bioenergetic fuel production is mediated by the metabolic reprogramming of both cancer and non-cancer cells in the tumor microenvironment (TME) (Wolpaw and Dang 2018 ). Not only metabolic cross-talk between tumor and stromal cells, metabolic reprogramming mediated by bacterial oncoproteins has been shown to directly contribute to carcinogenesis.…”