The role of targeted therapy in thymic carcinoma

Krishnan, Mridula; Ganti, Apar Kishor

doi:10.1177/1078155219852758

Cited by 7 publications

(5 citation statements)

References 41 publications

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“…The rarity of this tumor makes clinical trials difficult, and, thus, the development of new drugs is slow. Previous studies examined the effects of targeted therapies and immunomodulatory agents for thymic epithelial tumors (TET) (7). The findings obtained revealed that only sunitinib (an oral tyrosine kinase inhibitor of VEGFR, KIT, and PDGFR) and pembrolizumab (an immune checkpoint inhibitor) were active against TC (response rates of 26 and 22.5%, respectively) (8,9).…”

Section: Introductionmentioning

confidence: 99%

GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

et al. 2021

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Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ-aminobutyric acid from L-glutamic acid. GAD1 expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of GAD1 were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.

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Section: Introductionmentioning

confidence: 99%

GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

et al. 2021

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“…In our multicenter study on a series of 200 TET cases collected in the larger TET-TMA series built up, an extensive immunohistochemical angiogenesis-related investigation showed that VEGFR expression was associated with invasiveness and advanced stage (18). These data could provide biological support for the use of anti-angiogenetic drugs in TET treatment (67,68). An Italian clinical trial exploring the role of angiogenetic receptors in TET is currently in progress (48).…”

Section: Translational Research Perspectivementioning

confidence: 86%

Thymic Epithelial Tumors as a Model of Networking: Development of a Synergistic Strategy for Clinical and Translational Research Purposes

et al. 2020

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constant commitment and long-standing experience in diagnosis and research in TET. New perspectives opened up due to the establishment of national [the Italian Collaborative Group for ThYmic MalignanciEs (TYME)] and European reference networks such as EURACAN, for an empowered joint clinical action in adult solid rare tumors. The challenge we face still lies in the advancement of clinical and basic science in thymic epithelial malignancies.

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“…Primary thymic epithelial tumors are rare, but account for 20% of all mediastinal tumors [ 1 ]. While the overall incidence of thymic neoplasms has been estimated to be 0.13/100,000 (1% of all adult cancers), thymic carcinomas (TCs) are extremely rare and constitute only 0.06% of all malignancies [ 2 ], usually occurring in the fifth decade of life [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Does Myasthenia Gravis Affect Long-Term Survival in Thymic Carcinomas? An ESTS Database Analysis

Lococo¹,

Nachira²,

Chiappetta³

et al. 2022

Diagnostics

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Background: Thymic carcinoma is a rare and highly malignant tumor with a dismal prognosis, which occasionally coexists with myasthenia gravis (MG). This study aims to investigate the MG incidence on a surgical cohort of patients with thymic carcinoma and to explore its influence on long-term survival. Methods: the prospectively collected data from the ESTS database on thymic epithelial tumors were reviewed. Clinical, pathological, and survival information on thymic carcinoma were analyzed. Results: the analysis was conducted on 203 patients, with an equal gender distribution (96 males and 107 females). MG was detected in 22 (10.8%) patients, more frequently elderly (>60 years, p = 0.048) and male (p = 0.003). Induction therapy was performed in 22 (10.8%) cases. After surgery, 120 (59.1%) patients had a Masaoka stage II–III while complete resection (R0) was achieved in 158 (77.8%). Adjuvant therapy was performed in 68 cases. Mean follow-up was 60 (SD = 14) months. The 3-year, 5-year and 10-year survival rates were 79%, 75% and 63%, respectively. MG did not seem to influence long-term survival (5-year survival in non-MG–TCs 78% vs. 50% in MG–TCs, p = ns) as age < 60 years, female gender, early Masaoka stage, and postoperative radiotherapy did, conversely. Conclusions: myasthenia occurred in about 10% of thymic carcinomas and it did not seem to affect significantly the long-term prognosis in surgically treated thymic carcinoma-patients.

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The role of targeted therapy in thymic carcinoma

Cited by 7 publications

References 41 publications

GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

Thymic Epithelial Tumors as a Model of Networking: Development of a Synergistic Strategy for Clinical and Translational Research Purposes

Does Myasthenia Gravis Affect Long-Term Survival in Thymic Carcinomas? An ESTS Database Analysis

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