Targeted and immuno-based therapies in sarcoma: mechanisms and advances in clinical trials

Sarcomas represent a distinct group of rare malignant tumors with high heterogeneity. Limited options with clinical efficacy for the metastatic or local advanced sarcoma existed despite standard therapy. Recently, targeted therapy according to the molecular and genetic phenotype of individual sarcoma is a promising option. Among these drugs, anti-angiogenesis therapy achieved favorable efficacy in sarcomas. Inhibitors targeting cyclin-dependent kinase 4/6, poly-ADP-ribose polymerase, insulin-like growth factor-1 receptor, mTOR, NTRK, metabolisms, and epigenetic drugs are under clinical evaluation for sarcomas bearing the corresponding signals. Immunotherapy represents a promising and favorable method in advanced solid tumors. However, most sarcomas are immune "cold" tumors, with only alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma respond to immune checkpoint inhibitors. Cellular therapies with TCR-engineered T cells, chimeric antigen receptor T cells, tumor infiltrating lymphocytes, and nature killer cells transfer show therapeutic potential. Identifying tumor-specific antigens and exploring immune modulation factors arguing the efficacy of these immunotherapies are the current challenges. This review focuses on the mechanisms, advances, and potential strategies of targeted and immune-based therapies in sarcomas.