(P 60) EXPLORING METABOLIC REWIRING IN CHORDOMA

Objective: Chordoma is a rare, malignant bone tumor that arises from notochordal remnants within the axial skeleton. Primary tumors most commonly develop in the skull base or sacrum, and 30–40% metastasize to secondary sites such as the lungs or liver. In the United States, roughly 300 patients are diagnosed with chordoma every year (0.08 cases per 100,000 people). In these cases, individuals face a locally aggressive cancer that is extremely challenging to resect completely, prone to recurrence, and therapeutically resistant. These barriers to treatment, and the low 10-year survival rate (40%), highlight a drastic need for further research and development of new therapies to target chordoma. Metabolic reprogramming has been a fundamental area of cancer research in recent years, but chordoma metabolism is understudied and has not been fully utilized to aid in the development of novel therapies. Given the increasing interest in targeting cancer metabolism, understanding these metabolic alterations could reveal novel therapeutic targets not yet considered for treatment of chordoma.

Methods: Our lab has optimized an LC-MS/MS-based protocol for identifying 400 polar metabolites and 600 lipid species. We have used this protocol to determine the metabolic state of four different chordoma cell lines (U-CH2, UM-CHOR1, JHC7, and CH22) relative to two different fibroblast cell lines (LF and IMR90).

Results: Principal component analysis (PCA) of data obtained from our metabolomics panel demonstrated that chordoma cell lines possess a distinct metabolic profile compared to fibroblast controls. In addition to broad alterations across several key metabolic pathways, a subset of individual metabolites displayed statistically significant differences in abundance, further supporting a unique metabolic phenotype that may offer novel targets for therapeutic intervention.

Conclusion: We have identified several unique features in chordoma cell lines that warrant further investigation for their therapeutic capacity. Continued research into these differences will provide key insights into the biology of this malignancy and aid in therapy for those diagnosed.