Novel Treatments for Thymoma and Thymic Carcinoma

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Background

Thymoma and thymic carcinoma are rare tumors for which surgery forms the cornerstone of treatment. Chemotherapy and radiation therapy have a role in the management of advanced disease. Until recently not much was known about the molecular underpinnings of these diseases. This was due to the rarity of thymic tumors and the paucity of cell lines and animal models.
Due to rapid advances in genomic technology a large volume of data is emerging that might help in unraveling the genetic aberrations associated with thymic malignancies and explain the emergence of autoimmune diseases in some patients. The gene expression profile of a series of 34 patients with thymoma was analyzed and published in August 2012 (Badve et al, 2012). Also reported recently was the establishment and characterization of a cell line derived from a patient with World Health Organization-type AB thymoma (Gokmen-Polar et al, 2012). This is the first cell line that has been established from a type AB thymoma (four cell lines have been reported to date; three from patients with thymic carcinoma and one from a patient with a type B1 thymoma). An ongoing clinical trial is prospectively evaluating the molecular profile of thoracic malignancies including thymoma and thymic carcinoma (NCT01306045). The outline of this study was reported in abstract form at the American Society of Clinical Oncology (ASCO) annual meeting in 2012 (Lopez-Chavez et al, 2012; ASCO abstract #TPS7609). The role of the autoimmune regulator gene (AIRE) in thymic T-cell education has been described within the last decade. (Scarpino et al, 2007). It is thought that defective AIRE expression in thymoma may be responsible for the expansion of self-reactive T cell clones that result in the development of autoimmune diseases.
Not surprisingly, due to the poor understanding of thymoma tumor biology in previous years, the results of early studies of targeted agents for the treatment of thymoma and thymic carcinoma have been disappointing. Most of the small phase II studies that had evaluated epidermal growth factor receptor (EGFR)-directed therapy and imatinib in thymic malignancies showed no objective responses. A more recent study of the histone deacetylase (HDAC) inhibitor belinostat showed modest activity in patients with thymoma with a significant proportion of heavily-pretreated patients achieving disease stabilization (Giaccone et al, 2011). An ongoing phase II study of the insulin-like growth factor 1 receptor (IGF-1R) inhibitor, cixutumumab has also shown promising activity in patients with thymoma (Rajan et al, 2012; ASCO abstract #7033). A recent case series described responses to sunitinib in patients with thymic carcinoma (Strobel et al, 2010) and an ongoing clinical trial is evaluating this drug in patients with thymoma and thymic carcinoma (NCT01621568).
This section aims to highlight ongoing work that is focused on gaining greater insight into the biology of thymic tumors and the outcome of this research in the form of novel therapies for the treatment of thymoma and thymic carcinoma.

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