Research Outputs

focus on investigating the one of the major oncogenes in MYC, in regulating metabolism of tumour cells and their environment and defining metabolic vulnerabilities of tumours. We demonstrated that different isoforms of pyruvate kinase can sustain MYC-induced tumorigenesis. Only pyruvate kinase M2 isoforms had been previously considered tumour-specific. Treatment of colorectal cancer cells with a CDK4/6 inhibitor leads to increased expression of MYC and metabolic reprograming, including increased expression of glutaminase and activation of the mTOR patwhay. As the result, cells resistant to CDK4/6 inhibition become sensitive to inhibitors of MYC, glutaminase and mTOR. This demonstrates how metabolic reprogramming in response to cell cycle inhibitors can lead to new metabolic vulnerabilities. stable labelling human lung patients vivo slices we have demonstrated differential metabolism between two major subtypes of lung cancer, adenocarcinomas (AdCs) and squamous cell carcinomas (SCCs). We identified a 24-gene metabolic signature that is sufficient for the separation of SCCs from AdCs and non-cancerous lung. This suggested potential therapeutic targets specifically in SCCs. We identified Notch as a signalling pathway associated with the increased metabolic activities in SCCs. Identifying strategies to target the metabolic Nat DOI: Extreme multi-level flexibility of tumour metabolism is revealed. Demonstrates that 1) inhibition of enzyme isoforms expressed in a tumour can be compensated by an isoform expressed in normal tissue a tumour originated from; 2) inhibition of a metabolic pathway can be compensated by an alternative pathway, 3) inhibiting both glucose and glutamine catabolism, two major pathways feeding the Krebs cycle is required to significantly decrease the levels of Krebs cycle intermediates and inhibit tumour progression; 4) inhibiting production of metabolites like serine and fatty acids can be compensated by the uptake of these nutrients from the diet/blood stream.