43
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A Comprehensive Review on Solitary Fibrous Tumor: New Insights for New Horizons

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Abstract

          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.

          Related collections

          Most cited references149

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden

          Background High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. Methods In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome. We then describe the distribution of TMB across a diverse cohort of 100,000 cancer cases and test for association between somatic alterations and TMB in over 100 tumor types. Results We demonstrate that measurements of TMB from comprehensive genomic profiling are strongly reflective of measurements from whole exome sequencing and model that below 0.5 Mb the variance in measurement increases significantly. We find that a subset of patients exhibits high TMB across almost all types of cancer, including many rare tumor types, and characterize the relationship between high TMB and microsatellite instability status. We find that TMB increases significantly with age, showing a 2.4-fold difference between age 10 and age 90 years. Finally, we investigate the molecular basis of TMB and identify genes and mutations associated with TMB level. We identify a cluster of somatic mutations in the promoter of the gene PMS2, which occur in 10% of skin cancers and are highly associated with increased TMB. Conclusions These results show that a CGP assay targeting ~1.1 Mb of coding genome can accurately assess TMB compared with sequencing the whole exome. Using this method, we find that many disease types have a substantial portion of patients with high TMB who might benefit from immunotherapy. Finally, we identify novel, recurrent promoter mutations in PMS2, which may be another example of regulatory mutations contributing to tumorigenesis. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0424-2) contains supplementary material, which is available to authorized users.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial.

            Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis.

              The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. The novel bi-aryl urea BAY 43-9006 is a potent inhibitor of Raf-1, a member of the RAF/MEK/ERK signaling pathway. Additional characterization showed that BAY 43-9006 suppresses both wild-type and V599E mutant BRAF activity in vitro. In addition, BAY 43-9006 demonstrated significant activity against several receptor tyrosine kinases involved in neovascularization and tumor progression, including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor beta, Flt-3, and c-KIT. In cellular mechanistic assays, BAY 43-9006 demonstrated inhibition of the mitogen-activated protein kinase pathway in colon, pancreatic, and breast tumor cell lines expressing mutant KRAS or wild-type or mutant BRAF, whereas non-small-cell lung cancer cell lines expressing mutant KRAS were insensitive to inhibition of the mitogen-activated protein kinase pathway by BAY 43-9006. Potent inhibition of VEGFR-2, platelet-derived growth factor receptor beta, and VEGFR-3 cellular receptor autophosphorylation was also observed for BAY 43-9006. Once daily oral dosing of BAY 43-9006 demonstrated broad-spectrum antitumor activity in colon, breast, and non-small-cell lung cancer xenograft models. Immunohistochemistry demonstrated a close association between inhibition of tumor growth and inhibition of the extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation in two of three xenograft models examined, consistent with inhibition of the RAF/MEK/ERK pathway in some but not all models. Additional analyses of microvessel density and microvessel area in the same tumor sections using antimurine CD31 antibodies demonstrated significant inhibition of neovascularization in all three of the xenograft models. These data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                10 June 2021
                June 2021
                : 13
                : 12
                : 2913
                Affiliations
                [1 ]Fundacion Jimenez Díaz University Hospital, 28040 Madrid, Spain; nhindi@ 123456atbsarc.org
                [2 ]General de Villalba University Hospital, Collado Villalba, 28400 Madrid, Spain
                [3 ]Fundación Jiménez Díaz Institute for Medical Research (IIS/FJD), 28040 Madrid, Spain
                [4 ]Institute of Biomedicine of Seville (IBiS, CSIC, US and HUVR), 41013 Sevilla, Spain; Jose.mondaza@ 123456quironsalud.es (J.L.M.-H.); david.moura@ 123456usal.es (D.S.M.)
                Author notes
                Author information
                https://orcid.org/0000-0001-7350-6916
                https://orcid.org/0000-0002-5642-3796
                https://orcid.org/0000-0002-6514-2419
                https://orcid.org/0000-0002-5864-762X
                Article
                cancers-13-02913
                10.3390/cancers13122913
                8230482
                34200924
                8de5e4ac-b4af-40c8-b924-b9d86423af79
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 31 March 2021
                : 04 June 2021
                Categories
                Review

                solitary fibrous tumor,therapy,anti-angiogenics,tumor biology

                Comments

                Comment on this article