Synovial sarcoma diagnosis and management in the era of targeted therapies

Vlenterie, Myrella; Jones, Robin L.; Graaf, Winette T.A. van der

doi:10.1097/cco.0000000000000198

Cited by 27 publications

(28 citation statements)

References 59 publications

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“…Although all SS tumors harbor SS18-SSX fusion genes, there is a wide variety in clinical behavior and response to chemotherapy or targeted treatment within these tumors, emphasizing the role of additional factors in orchestrating SS progression (34). Our detection of ALK D2-17 in the Aska-SS cell line, and an ALK rearrangement in an ALK-immunopositive SS patient specimen, highlight ALK alterations as one such factor.…”

Section: Discussionmentioning

confidence: 93%

Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes

et al. 2017

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Despite intensive multimodal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling networks to reveal therapeutic targets and personalized treatment strategies. Here we applied mass spectrometry-based phosphoproteomic profiling to the largest and most heterogeneous set of sarcoma cell lines characterized to date and identified novel tyrosine phosphorylation patterns, enhanced tyrosine kinases in specific subtypes, and potential driver kinases. ALK was identified as a novel driver in the Aska-SS synovial sarcoma (SS) cell line via expression of an ALK variant with a large extracellular domain deletion (ALK D2-17 ). Functional ALK dependency was confirmed in vitro and in vivo with selective inhibitors. Importantly, ALK immunopositivity was detected in 6 of 43 (14%) of SS patient specimens, one of which exhibited an ALK rearrangement. High PDGFRa phosphorylation also characterized SS cell lines, which was accompanied by enhanced MET activation in Yamato-SS cells. Although Yamato-SS cells were sensitive to crizotinib (ALK/MET-inhibitor) but not pazopanib (VEGFR/PDGFR-inhibitor) monotherapy in vitro, synergistic effects were observed upon drug combination. In vivo, both drugs were individually effective, with pazopanib efficacy likely attributable to reduced angiogenesis. MET or PDGFRa expression was detected in 58% and 84% of SS patients, respectively, with coexpression in 56%. Consequently, our integrated approach has led to the identification of ALK and MET as promising therapeutic targets in SS.

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Section: Discussionmentioning

confidence: 93%

Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes

et al. 2017

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“…Interestingly, SS shows a considerable morphologic heterogeneity in which distinct histological subtypes can be distinguished: monophasic, containing spindle‐shaped mesenchymal cells; biphasic, containing both mesenchymal and well‐developed glandular epithelial cells; and the poorly differentiated subtype …”

Section: Discussionmentioning

confidence: 99%

Synovial sarcoma of the supraclavicular region causing a hemorrhagic shock

Halily¹,

Ballage²,

Ardhaoui³

et al. 2019

Clinical Case Reports

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“…Radiotherapy has also been recommended in stage III (T2, N0, M0, G3 OR any T, N1, M0, any G) disease as it can decrease the local recurrence. 17 Immunotherapy has substantial potential and provides a novel approach in SS combinatorial treatment. Promising results have been reported in adoptive T-cell therapy targeting immunogenic cancer testis antigen NY-ESO-1 in SS with wide expression of it.…”

Section: Discussionmentioning

confidence: 99%

Primary Synovial Sarcoma of the Orbit

Chen

2017

Ophthalmol Eye Dis

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Purpose:To describe the clinical, pathological, and immunohistochemical characteristics and therapies of a rare case of primary synovial sarcoma in the orbit.Design:Retrospective interventional case report.Participant:A 6-year-old girl with pathologically proven synovial sarcoma in the orbit. The diagnosis was confirmed by immunohistochemistry.Methods:The patient was treated with right lateral orbital and right temporal tumor resection, followed by chemotherapy. She was followed up every 3 months for 1 year.Results:The tumor was excised, and the patient received 5 courses of chemotherapy. She did well during the initial first-year follow-up with no recurrent signs.Conclusions:We reported the sixth case of primary synovial sarcoma in the orbit and the first case of a 6-year-old girl.

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Synovial sarcoma diagnosis and management in the era of targeted therapies

Cited by 27 publications

References 59 publications

Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes

Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes

Synovial sarcoma of the supraclavicular region causing a hemorrhagic shock

Primary Synovial Sarcoma of the Orbit

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