New targeted treatments for advanced sarcomas

Abstract

Purpose of reviewThe purpose of this review is to provide the rationale and results behind recent clinical trials regarding molecular-targeted agents for advanced sarcomas.Recent findingsTazemetostat, a first-in-class EZH2 inhibitor, was approved to treat advanced epithelioid sarcoma. In synovial sarcoma, the interaction between pathognomonic SS18-SSX fusion protein and the BAF complex has brought insight in using BRD9 inhibitors as a treatment based on synthetic lethality. MDM2 overexpression is an important mechanism to suppress p53 function, and MDM2 gene amplification is pathognomonic in well differentiated and dedifferentiated liposarcoma. Two MDM2 inhibitors, milademetan and BI907828, have both reached the optimal dosing and have shown promising efficacy in MDM2-amplified liposarcoma. Late-stage pivotal studies are ongoing for both of these MDM2 inhibitors. The co-amplification of CDK4 and MDM2 in liposarcoma also provided a rationale for CDK4/6 inhibitors as a potential therapy. Selinexor, an exportin-1 inhibitor, has shown single-agent activity in dedifferentiated liposarcoma and action in gastrointestinal stromal tumour in combination with imatinib. Lastly, a new formulation of mTOR inhibitor, nab-sirolimus, was recently approved for perivascular epithelioid cell tumour (PEComa).SummaryMolecular-guided precision medicine holds a bright future in bringing more active treatments for advanced sarcoma patients.

Low NT5DC2 expression predicts favorable prognosis and suppresses soft tissue sarcoma progression via ECM-receptor interaction pathway

“…At present, the main treatment of soft tissue sarcoma is surgical resection combined with preoperative or postoperative chemoradiotherapy [9] . In recent years, systemic therapy which refers to system anti-tumor therapy, containing chemotherapy, radiotherapy, targeted therapy and immunotherapy, is playing an increasingly important roles in the treatment of soft tissue sarcomas [10] , [11] , [12] , [13] . However, the improvement of prognosis in sarcoma patients is still limited.…”