Clinically-targetable vulnerabilities in cancer metabolism: A systematic review and meta-analysis
Objectives: To investigate the efficacy and safety of targeting cancer metabolic vulnerabilities with specific anticancer agents.
Method: The systematic review and meta-analysis entailed search on PubMed, Embase and Google Scholar databases for cohort-based studies or clinical trials which reported hazard ratio for overall survival and/or median overall survival of patients treated with metabolically-active anticancer drugs. Data was analysed using the Number Cruncher Statistical System version 11.
Results: There were 16 studies published between 1989 and 2018 that reported improvement in the overall survival (p=0.05) despite the reported significant heterogeneity across the studies (I2=70%). Exploiting amino acid metabolic vulnerabilities was associated with a favourable prognostic outcome (p=0.05), while targeting glycolysis and nucleic acid synthesis had no significant clinical importance (p>0.05).
Conclusion: There is an urgent need to develop future therapies relying on the synergistic actions of nucleotide biosynthesis, glycolysis and amino acid metabolism.
Key Words: Metabolic vulnerabilities, Cancer, Chemotherapy, Cell metabolism, Metabolic enzymes.