Immunologic and Targeted Molecular Therapies for Chordomas: A Narrative Review

Area of Science:

• Oncology
• Immunotherapy
• Sarcoma Research

Background:

• Chordomas are rare, aggressive bone sarcomas originating from notochordal remnants, predominantly affecting the spine.
• Current standard treatment involves surgical resection and radiotherapy, but long-term survival remains poor (approx. 30% at 20 years).
• Chordomas exhibit resistance to conventional chemotherapy, necessitating exploration of novel therapeutic strategies.

Purpose of the Study:

• To review and summarize recent advancements in immune-targeted therapies for chordoma.
• To discuss the clinical merits, trial outcomes, and toxicity profiles of novel immunotherapies and targeted agents.
• To provide an overview of treatments targeting vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) in chordoma.

Main Methods:

• Comprehensive literature review of preclinical and clinical studies on novel chordoma treatments.
• Focus on immunotherapies (antibody therapy, tumor vaccines) and targeted therapies (VEGFR, EGFR inhibitors).
• Analysis of reported progression-free survival, symptom relief, and adverse events from clinical trials.

Main Results:

• Early trials of novel immunotherapies have demonstrated potential for extended progression-free survival and symptom palliation in chordoma patients.
• Outcomes from larger clinical trials involving these novel therapeutic vectors have shown heterogeneous results.
• Targeted therapies, including VEGFR and EGFR inhibitors, are being investigated for their efficacy and safety in chordoma treatment.

Conclusions:

• Novel immune and targeted therapies represent a promising frontier in chordoma treatment, offering alternatives to conventional approaches.
• Further research and larger clinical trials are needed to optimize treatment strategies and overcome heterogeneity in patient responses.
• Understanding the specific molecular targets and immune profiles of chordomas is crucial for developing more effective therapies.