A comprehensive review on solitary fibrous tumor: New insights for new horizons

[Simple Summary] Solitary fibrous tumor (SFT) is a malignant condition that exhibits different clinical behaviors ranging from low to high aggressive SFT, with dedifferentiated SFT (DD-SFT) being the fastest-growing subtype. Even when surgery alone provides curation rates above 60%, recurrences do occur in a fraction of patients where surgery is unable to provide disease control. Among the systemic therapeutic options, antiangiogenic compounds have shown higher efficacy than chemotherapy by indirect comparisons. Furthermore, rotating different antiangiogenics, at the progression time, has been shown to be effective. The exception is DD-SFT since it is resistant to antiangiogenics but can respond to chemotherapy. This comprehensive review also analyzes the underlying molecular components that play a key role in SFT origin and aggressiveness. The discovery in 2013 of anomalous fusion genes between NAB2 and STAT6 was determinant to increase the knowledge on the molecular drivers in SFT that could be potential targets for future therapies. Solitary fibrous tumor (SFT) is a rare mesenchymal, ubiquitous tumor, with an incidence of 1 new case/million people/year. In the 2020 WHO classification, risk stratification models were recommended as a better tool to determine prognosis in SFT, to the detriment of “typical” or “malignant” classic terms. The risk for metastasis is up to 35–45%, or even greater, in series with a longer follow-up. Over the last few decades, advances in immunohistochemistry and molecular diagnostics identified STAT6 nuclear protein expression and the NAB2–STAT6 fusion gene as more precise tools for SFT diagnosis. Recent evidence taken from retrospective series and from two prospective phase II clinical trials showed that antiangiogenics are active and their sequential use from first line should be considered, except for dedifferentiated SFT for which chemotherapy is the best option. Since the fusion transcript driver’s first description in 2013, new insights have been brought on key molecular events in SFT. This comprehensive review mainly focuses on the superior efficacy of antiangiogenics over chemotherapeutic agents in SFT, provides the current knowledge of key molecules that could co-drive the SFT behavior, and suggests new target candidates that deserve to be explored in preclinical and clinical research in SFT. The authors would also like to thank the SELNET project. SELNET has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 825806. Furthermore, the authors would like to thank the Instituto de Salud Carlos III (ISCIII)—Fondo Europeo de Desarrollo Regional (FEDER), project reference PI18/01728. David S. Moura is the recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155). José L. Mondaza-Hernandez is the recipient of a PFIS predoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (FI19/00184).