Systemic Therapy, Trials, and Future Directions for Chordoma of the Spine

Surgical resection and adjuvant radiation are the mainstays of treatment for patients with chordoma. However, these local therapies are easily exhausted during the treatment of chordoma of the axial skeleton in patients with advanced, recurrent, or metastatic disease. There is currently no approved standard of care first-line systemic therapy for the systemic treatment of chordoma. Conventional cytotoxic chemotherapy has been shown to have few benefits for the treatment of chordoma. Therefore, efforts to improve and expand systemic treatment options have focused on the identifying and targeting genetic, epigenetic, cellular signaling, and immunologic characteristics of chordoma cells. In this chapter, we review preclinical and clinical data from the use of molecularly targeted therapies for the treatment of chordoma, including those targeted against receptor tyrosine kinases, intracellular signaling pathways, the cell cycle, and epigenetic regulation of gene control. Finally, we detail ongoing efforts to use immunotherapy strategies to treat patients with chordoma.