Abstract

Soft tissue sarcomas (STS), a diverse group of mesenchymal malignancies, present a diagnostic mystery due to their heterogeneity and the restrictions of traditional methods. Invasive biopsies offer a stationary outline of a dynamic process, failing to capture the tumor’s evolving metabolic landscape. This opinion conceives that untargeted metabolomics, specifically when applied to liquid biopsies, offers an exemplar shift in STS diagnostics. By cross-examining the circulating metabolome, we can gain real-time insights into tumor behavior, treatment response, and metastatic potential. This method moves beyond static genetic markers, revealing a metabolic illusion that replicates the tumor’s adaptation to its microenvironment. Important metabolites, such as ketone bodies, choline derivatives, and purines, emerge as potential biomarkers, offering a preview into altered energy metabolism, membrane dynamics, and cell proliferation. Integrating metabolomic data with genetic profiling provides a universal understanding of STS biology, paving the way for earlier detection, personalized therapies, and improved patient outcomes. A call for collaborative action is essential to harness the full potential of untargeted metabolomics in the fight against STS.

Keywords: Cancer metabolomics; Soft-tissue sarcomas; Oncogenic-physiology; Personalized therapy; Liquid biopsies

Abbreviations: STS: Soft Tissue Sarcomas; GC-MS: Gas Chromatography-Mass Spectrometry; LC-MS: Liquid Chromatography-Mass Spectrometry; LC-MS/MS: Liquid Chromatography with Tandem Mass Spectrometry (also known as LC-MS2); MRI: Magnetic Resonance Imaging; FISH: Fluorescence In Situ Hybridization; RNA-seq: RNA Sequencing; 18F-FDG: 18-FluoroDeoxyGlucose; EWSR1-FLI1: Ewing Sarcoma; RNA Binding Protein 1-Friend Leukemia Integration; Transcriptional Activator; FUS-CHOP: Fusion-CCAAT/Enhancer Binding Protein Homologous Protein; SS18-SSX: Synovial Sarcoma Translocation; Chromosome 18-Synovial Sarcoma X breakpoint; COL1A1-PDGFB: Collagen Type I Alpha 1 Chain-Platelet-Derived Growth Factor Subunit B; MDM2: Mouse Double Minute 2; CDK4: Cyclin-Dependent Kinase 4; TP53: Tumor Protein P53; RB1: Retinoblastoma 1; PIK3CA: Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha; AKT: Protein Kinase B; mTOR: Mammalian Target of Rapamycin; CT: Computed Tomography; US: Ultrasound; PET: Positron Emission Tomography; ATP: Adenosine Triphosphate; GTP: Guanosine Triphosphate; DNA: Deoxyribonucleic Acid; RNA: Ribonucleic Acid; ctDNA: Circulating tumor DNA; CTCs: Circulating tumor cells