Targeted therapies and checkpoint inhibitors in sarcoma

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Sarcomas are rare mesenchymal malignancies with over 100 subtypes, often diagnosed with existing micrometastasis.
• Current treatments rely on surgery, chemotherapy, and radiotherapy, with limited success from genetic insights.
• Immunotherapy has advanced in solid tumors but shows restricted impact in sarcoma.

Approach:

• This review discusses common immunotherapy strategies for sarcomas, including immune checkpoint inhibitors, targeted therapy, and cytokine therapy.
• It examines the efficacy of the programmed cell death (PD)-1/PD-1L axis and TNF-related apoptosis-inducing ligand (TRAIL).
• Emerging strategies targeting macrophage migration inhibitory factor (MIF) are also considered.

Key Points:

• The PD-1/PD-1L axis and TRAIL have not replicated successes seen in other solid tumors.
• Certain sarcoma subtypes, like liposarcoma and undifferentiated pleomorphic sarcoma, show promise with combination immunotherapies.
• Targeted therapy against MIF presents a potential future avenue for sarcoma treatment.

Conclusions:

• Despite limited success, immunotherapy holds potential for sarcoma treatment, particularly in combination regimens.
• Further investigation into novel targets like MIF is warranted for developing advanced sarcoma therapies.
• Personalized treatment strategies based on sarcoma subtypes and genetic profiles are crucial for improving outcomes.