Cancer Metabolism and Therapeutic Strategies

Cancer cells rewire their metabolic pathways to support rapid proliferation, survival under stress and resistance to therapy. Unlike normal tissues, many tumours exhibit enhanced glucose uptake and lactate production even in the presence of oxygen, a phenomenon known as the Warburg effect. Beyond aerobic glycolysis, malignant cells exploit glutamine as a nitrogen and carbon source, engage the pentose phosphate pathway to generate reducing equivalents, and activate lipid biosynthesis and fatty acid oxidation to fuel membrane synthesis and energy demands. This metabolic plasticity allows adaptation to hypoxia, nutrient limitation and immune surveillance. Therapeutic strategies aimed at metabolic vulnerabilities include inhibition of key enzymes in glycolysis and glutaminolysis, blockade of lipid metabolic pathways, modulation of redox balance, and exploitation of metabolic checkpoints such as mTOR. Combinations of metabolic inhibitors with conventional chemotherapy or targeted agents have shown promise in preclinical models, while non-invasive metabolic imaging and serum metabolite profiling offer potential for early diagnosis and monitoring of treatment response. A comprehensive understanding of tumour metabolism is now guiding the development of precision therapies that selectively disrupt cancer-specific metabolic circuits without undue toxicity to normal tissues.

Research from Nature Portfolio

Recent studies have elucidated how cysteine metabolism underpins ovarian cancer adaptation to hypoxia and resistance to platinum-based therapy. Ovarian carcinoma cell lines with acquired carboplatin resistance show a heightened dependency on extracellular cysteine, which feeds both hydrogen sulphide production and glutathione synthesis. Under hypoxic conditions, tumour cells exploit cysteine recycling to maintain redox homeostasis, promote survival and evade apoptosis. Analysis of patient serum revealed elevated levels of free cysteine and homocysteine in malignant cases compared with benign controls, whereas reduced glutathione levels correlated with advanced disease. Importantly, the degree of protein S-cysteinylation distinguished malignant from benign lesions, suggesting that measurement of circulating cysteine species may serve as a non-invasive biomarker for early detection, prognosis and real-time assessment of therapeutic efficacy.

Cancer Metabolism and Therapeutic Strategies publication trend

The graph below shows the total number of articles in cancer metabolism and therapeutic strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Warburg effect: The propensity of cancer cells to preferentially convert glucose to lactate under aerobic conditions.

Glycolysis: A sequence of enzymatic reactions that breaks down glucose to pyruvate, yielding ATP and NADH.

Glutaminolysis: The metabolic pathway by which glutamine is converted into intermediates for energy production and biosynthesis.

Redox homeostasis: The balance between production and detoxification of reactive oxygen species to maintain cellular function.

mTOR (mechanistic target of rapamycin): A central kinase that integrates nutrient and growth signals to regulate metabolism and cell growth.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that can damage cellular components but also act as signalling mediators.

References

1. Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis. Journal of Translational Medicine (2024).
2. Metabolic Reprogramming of Chemoresistant Cancer Cells and the Potential Significance of Metabolic Regulation in the Reversal of Cancer Chemoresistance. Metabolites (2020).
3. Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity. Scientific Reports (2018).
4. Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism. npj Precision Oncology (2017).