Understanding Tumour Metabolic Reprogramming with Metabolomics

Abstract

Abstract Although cancer is well recognised as a genetic disease, there is an emerging awareness that many of these genetic mutations promote an established hallmark of tumour cells – metabolic reprogramming. And while the connection between oncogenic signalling and the metabolic reprogramming of tumour cells (in hindsight) is highly intuitive, how to expand on this knowledge and capitalise on it for therapeutic gain is yet to be fully actualised. An emerging opportunity to expand this possibility involves taking advantage of the fact that diverse genetic alterations in tumour cells converge to the shared features of metabolic reprogramming. Therefore, these features could offer a common means to target the tumour irrespective of the mutational status. However, in all likelihood, the most selective and efficacious treatments will emerge from combining data to specifically define the genetic and metabolic features of a tumour with modern genomic and metabolomic technologies. Conceptually, genotyping and metabotyping can be combined in an effort to define efficacious first line dual‐targeted combinations. Although there are many practical considerations and challenges to achieve this end, the premise will be described through a number of preclinical examples that begin to offer an illustration of this possibility. Key Concepts: Oncogenes and tumour suppressors directly regulate metabolic reprogramming. Metabolic reprogramming supports tumour energetics, biosynthesis and survival. Metabolic targets present viable options for therapeutic development. Global metabolite profiling provides knowledge into tumour signalling pathway dysregulation. Metabolic reprogramming contributes to therapeutic resistance/sensitivity. Understanding malignant cell metabolism affords greater insight into optimal drug combination strategies. Metabolomics combined with genotyping offers an opportunity to advance personalised cancer medicine.