Biology and management of clear cell sarcoma: state of the art and future perspectives

Introduction: Clear cell sarcoma (CCS) is an aggressive tumor, typically developing in tendons or aponeuroses. The outcome of this orphan disease is poor, with 5-year and 10-year survival rates of localized CCS around 60-70% and 40-50%. Once the disease has metastasized, it is usually fatal due to its chemotherapy-resistant nature. Systemic treatment options are poorly standardized and the use of chemotherapy is based on weak scientific evidence.Areas covered: In this review, we systematically discuss the current scientific evidence for the systemic treatment of CCS, including tyrosine kinase inhibitors, immunotherapy and MET inhibitors.Expert commentary: Recent insights in the biology of CCS have identified new potential therapeutic targets, which should be tested in prospective clinical trials. Whenever possible, patients with metastatic CCS should be included in clinical trials with good biological rationale. Innovative trial methodology and new regulatory mechanisms are required to provide patients with uncommon cancers with active drugs.