Clinical challenges and therapeutic strategies in chordoma: Translating molecular insights into patient care.

Chordoma is a rare, locally aggressive bone tumor originating from notochordal remnants. Despite advances in surgical and radiation-based approaches, effective systemic therapies remain limited, and recurrence rates are high. This chapter explores the current clinical landscape of chordoma management with an emphasis on the integration of molecular insights into therapeutic decision-making. In particular, we highlight emerging strategies targeting brachyury and receptor tyrosine kinases, as well as promising immunotherapies, including PD-1/PD-L1 immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. We further underscore the pivotal role of institutional and multi-center biobanking efforts in enabling biomarker discovery, enhancing diagnostic accuracy, and facilitating patient prognostication. Alongside these efforts, clinical trial development and public health considerations provide a comprehensive overview of the present scope and future potential of precision medicine in chordoma. By emphasizing the translational potential of molecular profiling together with advances in the clinical, institutional, and public health infrastructures that support its implementation, this chapter outlines a pathway toward more personalized and effective care for patients with chordoma.