Untargeted Mass Spectrometry Reveals Consistent Metabolic Shifts In Fibroblasts Treated With Cancer Therapeutics

This record contains the published article, “Untargeted Mass Spectrometry Reveals Consistent Metabolic Shifts in Fibroblasts Treated with Cancer Therapeutics,” originally published in the National High School Journal of Science in 2026. Fibroblasts are integral to tissue maintenance and wound healing. However, in the tumor microenvironment, activated fibroblasts can promote cancer progression through the extracellular matrix via the secretion of cytokines that recruit and polarize immune cells and the modification of drug penetration and paracrine signaling. Fibroblasts are widespread across the body and are often subject to chemotherapeutic agents, yet their metabolic response to these agents remains unclear. While cancer therapeutics are intended to influence cancerous cells solely, evidence demonstrates that chemotherapeutic agents, including doxorubicin, often modify fibroblast metabolism and signaling mechanisms in sublethal concentrations, including the alteration of TGF-β signaling pathways and myofibroblast differentiation. This study’s goal is to understand the effects of three anti-cancer agents on the metabolism of mouse-derived fibroblast cells: 2-deoxyglucose, which inhibits glycolysis; 5-fluorouracil, which inhibits pyrimidine synthesis; and doxorubicin, which is an anthracycline chemotherapeutic. The analysis of untargeted LC-MS uncovered that treatment-induced metabolic shifts include the common feature rt/mz 7.78/453.17, tentatively identified as 5α-androstan-3β ,17α-diol disulfate, along with features linked to lipid, steroid, redox, mitochondrial, and polyamine metabolism. The consistent feature-based shifts in all treatment groups show how the introduction of anti-cancer agents can alter fibroblast metabolomic patterns, but the significant metabolites found require future confirmation through MS/MS fragmentation. This study emphasizes that stromal metabolism could play an integral role in the