Metabolic profiles of melanoma patients and PDX models

Patient-derived xenografts (PDXs) are frequently used as preclinical
models, but their recapitulation of tumor metabolism in patients has not
been closely examined. We developed a parallel workflow to analyze
[U-13C]glucose tracing and metabolomics from patient melanomas and matched
PDXs. Melanomas from patients have substantial TCA cycle labeling, similar
to levels in human brain tumors. We observed differences in TCA cycle
labelling among PDXs that were similar to differences we observed among
the same melanomas in patients, but PDXs had higher labeling in glycolytic
intermediates than the same melanomas in patients. We observed consistent
metabolic alterations among PDXs and patient tumors that reflected
species-specific differences in diet, enzyme expression and other factors.
Despite these differences, most of nearly 200 PDXs retained a “metabolic
fingerprint” that resembled the same melanomas in patients. PDX metabolism
was also largely retained over at least 6 passages. We conclude that
awareness of both high- and low-fidelity features will help optimize the
use of PDXs to study human cancer metabolism.