Abstract
Simple SummarySarcomas constitute a rare and heterogeneous group of malignant neoplasms, encompassing over 100 distinct histological subtypes. These tumors account for less than 1% of all adult malignancies and have propensity for diagnosis in younger individuals. Soft tissue sarcomas (STSs), originating from mesodermal tissue, can arise in a variety of structures including muscles, adipose tissue, and peripheral nerves. While anthracycline-based chemotherapy remains the cornerstone of treatment, ongoing advancements in the molecular biology of STSs are significantly enhancing our understanding of these complex tumors. These discoveries have facilitated the development of more tailored therapeutic strategies, including targeted therapies and immunotherapies, with the goal of improving treatment responses and long-term survival outcomes. However, survival rates remain suboptimal, particularly in patients with advanced-stage disease. Recent therapeutic innovations emphasize histology-specific treatment approaches, which necessitate a comprehensive integration of pathological, immunohistochemical, and molecular profiling to guide clinical decision-making. This review aims to provide an overview of the current systemic treatment options for STSs (except gastrointestinal stromal tumors), highlight recent progress in the field, and discuss emerging avenues for future therapeutic strategies in sarcoma management.AbstractSoft tissue sarcomas [STSs] are rare tumors of mesodermal origin that arise in diverse tissues such as muscles, fat, and nerves. There are over 100 subtypes of STS, each with distinct clinical behaviors and responses to treatment. Recent advances in treatment have moved towards histology-specific approaches, emphasizing the integration of pathological, immunohistochemical, and molecular features to guide treatment. Localized STS is primarily treated with surgery, often supplemented by neoadjuvant or adjuvant radiation and/or chemotherapy. However, about half of patients with localized disease will progress to an advanced stage, which is typically managed with systemic therapies including anthracycline-based chemotherapy such as doxorubicin or epirubicin. Despite these treatments, the survival rates for most subtypes of advanced metastatic STS remain relatively low. While anthracycline-based chemotherapy remains the mainstay of treatment, ongoing research into the biology of STSs is enhancing our understanding and approach to these complex tumors with an expansion beyond chemotherapy to include targeted therapy and immunotherapy to improve response rates and survival outcomes. This review focuses on STS other than gastrointestinal stromal tumors [GISTs], examines the current systemic treatment strategies, highlights recent advances, and explores future directions in the systemic therapy of sarcoma patients.