Synovial Sarcoma: Advances in Diagnosis and Treatment Identification of New Biologic Targets to Improve Multimodal Therapy

Beaino, Marc El; Araujo, Dejka M.; Lazar, Alexander J.; Lin, Patrick P.

doi:10.1245/s10434-017-5855-x

Cited by 60 publications

(51 citation statements)

References 123 publications

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“…The evidence about the underlying mechanisms of action of the other drugs is insufficient, however. For example, synovial sarcoma, which is known as the characteristic chromosomal translocation of t(X;18)(p11.2;q11.2) [16], is sensitive to ifosfamide, and ifosfamide-containing regimens are preferably prescribed for synovial sarcoma patients in clinical practice [17,18], even though there have been no results of prospective randomized clinical trials. The combination of gemcitabine and docetaxel used in the phase 3 trial described above was first examined in a phase 2 trial of leiomyosarcoma, which included a high percentage of cases of uterine origin [19].…”

Section: Histology-based Chemotherapy Investigations Based On Clinicamentioning

confidence: 99%

Precision Medicine in Soft Tissue Sarcoma Treatment

Nakano

Takahashi

2020

Cancers

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Soft tissue sarcoma (STS) is a rare component of malignant diseases. STS includes various histological subtypes, and there are some important differences among the different histological subtypes regarding the mutation profile and sensitivity to antitumor agents. Many clinical trials of STS incorporating many different histological subtypes in various populations have been conducted; it is difficult to compare the findings and make conclusions about clinical efficacy. Targeted therapies focusing on specific histological subtypes and precision therapy focusing on the specific genetic mutation(s) of each STS patient are being investigated. Since STS patients are a small population, new clinical trial designs are required to evaluate and establish new targeted therapies for each histological subtype that has a limited number of patients, and preclinical investigations are needed to detect targetable mutations. Now that cancer genome profiling is used in clinical practice, it is urgently necessary to connect the genome profiling data obtained in clinical settings to the optimal clinical treatment strategies. Herein we review the development and challenges of precision therapy in the management of STS patients.

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Section: Histology-based Chemotherapy Investigations Based On Clinicamentioning

confidence: 99%

Precision Medicine in Soft Tissue Sarcoma Treatment

Nakano

Takahashi

2020

Cancers

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“…Diagnosis of synovial sarcoma is based on a combination of findings, including its characteristic morphology, immunohistochemical profile, and identification of the driver translocation [5]. Despite being the gold standard in establishing diagnosis, SS18-SSX detection can be challenging in rare cases, since some tumors (<2% of cases) can be driven by other less common cryptic and genetic rearrangements [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of TLE1 in Synovial Sarcoma: A Systematic Review and Meta-Analysis

Beaino

Jupiter

Assi

et al. 2020

Sarcoma

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Background. Synovial sarcoma can present morphologically in multiple forms, including biphasic and monophasic subtypes. As a result, the histological diagnosis can sometimes be challenging. Transducin-Like Enhancer 1 (TLE1) is a transcriptional corepressor that normally is involved in embryogenesis and hematopoiesis but is also expressed in certain tumors. This systematic review examines the potential role of TLE1 as a diagnostic biomarker for the synovial sarcoma. Materials and Methods. A literature review and meta-analysis were conducted using the electronic databases Pubmed, the Cochrane Library, and Google Scholar. Thirteen studies met our eligibility criteria and were selected for in-depth analysis. Results. The mean sensitivity and specificity of TLE1 in detecting synovial sarcoma were 94% (95% CI 91%–97%) and 81% (95% CI 72%–91%), respectively, when all studies were aggregated together. The mean positive predictive value (PPV) of TLE1 was 75% (95% CI 62%–87%), whereas the negative predictive value (NPV) was 96% (95% CI 93%–98%). Conclusion. TLE1 is a sensitive and specific marker for synovial sarcoma that can aid in its diagnosis. Due to its involvement in several relevant signaling pathways, TLE1 might have direct relevance to the pathophysiology of the disease.

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“…However, the design of direct inhibitors for wild-type and fusion transcription factors can be attributed in part to the large protein-protein interaction interfaces and absence of deep protein pockets that are common targetable sites for drug design [13,14]. Only a few molecules were Phase I-II clinical trials [132] Tenosinovial giant cell tumor t(1; 2) (p13; q35-37)…”

Section: Inhibition Of Target Oncogenic Protein Expression Ormentioning

confidence: 99%

Current Approaches for Personalized Therapy of Soft Tissue Sarcomas

Кирсанов

Lesovaya

Fetisov

et al. 2020

Sarcoma

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Soft tissue sarcomas (STS) are a highly heterogeneous group of cancers of mesenchymal origin with diverse morphologies and clinical behaviors. While surgical resection is the standard treatment for primary STS, advanced and metastatic STS patients are not eligible for surgery. Systemic treatments, including standard chemotherapy and newer chemical agents, still play the most relevant role in the management of the disease. Discovery of specific genetic alterations in distinct STS subtypes allowed better understanding of mechanisms driving their pathogenesis and treatment optimization. This review focuses on the available targeted drugs or drug combinations based on genetic aberration involved in STS development including chromosomal translocations, oncogenic mutations, gene amplifications, and their perspectives in STS treatment. Furthermore, in this review, we discuss the possible use of chemotherapy sensitivity and resistance assays (CSRA) for the adjustment of treatment for individual patients. In summary, current trends in personalized management of advanced and metastatic STS are based on combination of both genetic testing and CSRA.

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Synovial Sarcoma: Advances in Diagnosis and Treatment Identification of New Biologic Targets to Improve Multimodal Therapy

Cited by 60 publications

References 123 publications

Precision Medicine in Soft Tissue Sarcoma Treatment

Precision Medicine in Soft Tissue Sarcoma Treatment

Diagnostic Value of TLE1 in Synovial Sarcoma: A Systematic Review and Meta-Analysis

Current Approaches for Personalized Therapy of Soft Tissue Sarcomas

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