Isotope-Guided Analytical Strategies for Assessing Metabolic Networks in Cancer

Dear Colleagues,

The reprogramming of the cancer metabolism is central to the process of malignant transformation. A growing repertoire of flux analysis techniques have provided new insights into our understanding of the cancer metabolism in primary and metastatic settings, as well as revealing the complex metabolic interplay between cancer cells and other cell types in the tumor microenvironment. Stable isotope-guided analysis, whether targeted or untargeted, has enabled fundamental discoveries in the cancer metabolism. Hypothesis-driven approaches that interpret targeted metabolite ¹³C, ¹⁵N, ¹⁸O or ²H labeling patterns have uncovered key nutrient dependencies in tumor and immune cells, revealed metabolic reprogramming driven by oncogenic mutations, and led to the identification of unique metabolic adaptations that enable the continuity of energy generation, while fostering enhanced biosynthetic pathways. In contrast, unsupervised isotope-tracing metabolomics, especially with ultra-high resolution mass spectrometry systems, can measure metabolome-wide shifts in pathways, which is discovery-based and hypothesis-generating without a defined model. ¹³C metabolic flux analysis (¹³C-MFA) leverages measured extracellular uptake and secretion rates, as well as isotopic labeling with an assumed metabolic network model, in order to find the most likely solution of fluxes.¹³C-MFA can be aided by approaches that integrate the constraint-based modeling of metabolic flux, which itself can be used for flux prediction for cancer mechanisms using genome-scale human metabolic network reconstructions. This issue will cover how advances in stable isotope and computational flux methodologies have yielded new insights into metabolic networks within the tumor niche, and then detail how emerging flux methods at the cutting-edge of isotope flux analysis are being applied to examine compartmental and spatial metabolic interactions within tumors.

Dr. Irwin J. Kurland
Prof. Dr. Henri Brunengraber
Dr. Alison E. Ringel
Dr. Yunping Qiu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.