Molecular characterization and experimental models of chordoma: Foundations for rational therapy development

Advancing therapeutic strategies for chordoma requires a deep molecular understanding of tumor biology, supported by robust and reproducible experimental models. This chapter reviews recent progress in the development of in vitro and in vivo chordoma systems, including novel cell lines, genetically engineered models, and patient-derived xenografts. We detail the molecular and epigenetic features that underpin chordoma pathogenesis and resistance to therapy. Special attention is given to the design and testing of combinatorial therapeutic approaches-including immunotherapies, epigenetic modulators, and hydrogel-based drug delivery systems-that target distinct molecular vulnerabilities. Together, these innovations provide a translational framework for next-generation therapies tailored to the unique biology of chordoma.