Challenges and Opportunities in Cancer Metabolomics

Abstract

Challenges in metabolomics for a given spectrum of disease are more or less comparable, ranging from the accurate measurement of metabolite abundance, compound annotation, identification of unknown constituents, and interpretation of untargeted and analysis of high throughput targeted metabolomics data leading to the identification of biomarkers. However, metabolomics approaches in cancer studies specifically suffer from several additional challenges and require robust ways to sample the cells and tissues in order to tackle the constantly evolving cancer landscape. These constraints include, but are not limited to, discriminating the signals from given cell types and those that are cancer specific, discerning signals that are systemic and confounded, cell culture‐based challenges associated with cell line identities and media standardizations, the need to look beyond Warburg effects, citrate cycle, lactate metabolism, and identifying and developing technologies to precisely and effectively sample and profile the heterogeneous tumor environment. This review article discusses some of the current and pertinent hurdles in cancer metabolomics studies. In addition, it addresses some of the most recent and exciting developments in metabolomics that may address some of these issues. The aim of this article is to update the oncometabolomics research community about the challenges and potential solutions to these issues.

Genome variation in colorectal cancer patient with liver metastasis measured by whole-exome sequencing

“…The process of LM of CRC is extremely complex, involving many tumor-related molecules, which are induced and regulated by their respective specific signaling pathways. With the continuous progress of all kinds of research techniques in recent years, a growing body of evidence has shown that tumor development and metastasis are related to the cancer genome (16), transcriptome (17), epigenetics (18), proteome (19), metabolome (20), and tumor microenvironment (21) interaction cross-regulation of a dynamic complex process.…”

Advances on diagnostic biomarkers of pancreatic ductal adenocarcinoma: A systems biology perspective

“…The authors reported that 10 metabolites were different between early-stage PDAC and IPMN, and that PCA could be a useful tool for early diagnosis of PDAC. Challenges in metabonomics include compound annotation, identification of unknown constituents, accurate measurement of metabolite abundance, and analysis of high-throughput metabonomics data [55] . Additionally, metabonomics in cancer research specifically requires robust ways to collect samples in order to precisely and effectively profile the heterogeneous tumor environment [55] .…”

“…Challenges in metabonomics include compound annotation, identification of unknown constituents, accurate measurement of metabolite abundance, and analysis of high-throughput metabonomics data [55] . Additionally, metabonomics in cancer research specifically requires robust ways to collect samples in order to precisely and effectively profile the heterogeneous tumor environment [55] . Overall, metabonomics allows researchers to identify novel biomarkers that were not previously known to be involved in PDAC carcinogenesis and development.…”

In situ Metabolic Profiling of Ovarian Cancer Tumor Xenografts: A Digital Pathology Approach

“…Advanced technologies, including metabolomics (8) and metabolic flux analysis (9), are key to decode the heterogeneous metabolic preferences and dependencies of tumors in vivo, but they can only be performed in a very limited number of patients given the high costs of the equipment and the level of specialization of personnel involved in this type of analysis. Moreover, these techniques do not enable to study intra-tumor metabolic heterogeneity as they assess levels of metabolites in whole tumor lysates or track the incorporation of a labeled substrate into downstream metabolites.…”