Molecular, Genetic and Immunomodulatory Mechanisms in Soft Tissue Sarcoma

Dear Colleagues,

Soft tissue sarcomas (STS) are a heterogeneous group of rare malignant neoplasms arising within embryonic mesenchymal tissues during the process of differentiation into cartilage, muscle, blood vessels, nerves, and fat. Diagnosis of sarcoma is based on morphology, immunohistochemistry, and clinicopathological correlation. A better understanding of the molecular biology of pathogenesis is fundamental, as STSs are distinguished by specific molecular aberrations, such as somatic mutations, deletions, gene amplifications, reciprocal translocations, and complex karyotypes. Molecular studies have been critical in providing refinements to morphologic sarcoma classification, at times very challenging, while contributing to diagnostic information, prognostic stratification and predictive insights concerning specific therapies.

All molecular and genetic discoveries have led to a better understanding of the modern concepts of cancer biology, including molecular signals driving tumor growth and permanence, and the molecular pathways involved leading to treatment strategy options for STS. Sustained growth, the evasion of growth suppressors, resistance to death, induction of angiogenesis, and the ability to invade and spread are fundamental tumor characteristics, all of which have underlying molecular correlates that scientists are beginning to uncover and comprehend. However, in addition to molecular and genetic findings, other determinants, such as genomic instability, immunological profile, tumor-promoting inflammation, and deregulation of cellular energy pathways have a critical role in the aggressiveness of sarcomas. Only 15% of STS patients respond in immunotherapy trials; there are no biomarkers predicting the response of STS to checkpoint blockade therapies yet. Therefore, unraveling immunomodulatory mechanisms in STS have the potential to unveil essential insights to immunotherapy approaches. 

This Special Issue of IJMS intends to bring together high-quality publications covering several innovating insights on the molecular, genetic and immunomodulatory mechanisms, leading to a better understanding of STS development. These novel aspects may ultimately improve the clinical management of both adult and pediatric STS patients, providing a better clinical understanding, developing safer and more potent targeted therapies, and driving new initiatives to improve their final outcome.

Dr. Gasparini Patrizia
Guest Editor

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