Clinically-targetable vulnerabilities in cancer metabolism: A systematic review and meta-analysis.

OBJECTIVE

To investigate the efficacy and safety of targeting cancer metabolic vulnerabilities with specific anticancer agents.

METHODS

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 metabolicallyactive 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).

CONCLUSIONS

There is an urgent need to develop future therapies relying on the synergistic actions of nucleotide biosynthesis, glycolysis and amino acid metabolism.