Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors

Molecular aberrations underlying thymic malignancies are poorly understood and lack valid preclinical models. Their rarity and complexity hinders investigations of causes and therapy development. EGFR, KIT, IGF1R, VEGF-A/VEGF-B/VEGF-2, and TrkA have been reported to be overexpressed. EGFR overexpression is associated with higher stage, IGF1R overexpression has poor prognostic value. Thymic epithelial tumors (TETs) are rare primary mediastinal tumors arising from thymic epithelium. Their rarity and complexity hinder investigations of their causes and therapy development. Here, we summarize the existing knowledge regarding medical treatment of these tumors, and thoroughly review the known genetic aberrations associated with TETs and the present status of potential biological treatments. Epidermal growth factor receptor (EGFR), stem-cell factor receptor, insulin-like growth factor-1 receptor (IGF1R), and vascular endothelial growth factors (VEGF-A, VEGF-B, and VEGF-2) are overexpressed in TETs. EGFR overexpression in TETs is associated with higher stage, and IGF1R overexpression has poor prognostic value. Data indicate that anti-IGF1R monoclonal antibodies, and inhibitors of angiogenesis, somatostatin receptors, histone deacetylase, mammalian target of rapamycin, and cyclin-dependent kinases may be active against TETs. Continued investigations in this field could lead to advancement of targeted and biological therapies for TETs.