The Multidisciplinary Approach to Thymoma: Combining Molecular and Clinical Approaches

Abstract

Thymomas are rare epithelial tumors that display significant heterogeneity. Thymomas are usually indolent; however, thymic carcinomas are typically invasive with a high risk of relapse and death. Current treatment approaches are primarily based on clinical stage. Surgery is the mainstay for treatment of early stage disease, whereas multimodality therapy is required for advanced disease. The most important prognostic factors are stage and histology; however, increasing recognition of disease heterogeneity has led to recent exploration of underlying molecular mechanisms. Molecular characterization of thymic tumors may offer strategies to improve diagnosis, therapy, and prognosis. This article describes recently identified molecular characteristics of thymoma and thymic carcinoma that may potentially impact disease classification, targeted therapeutic decision making, and design of future clinical trials.

Thymoma Patients Treated in a Phase I Clinic at MD Anderson Cancer Center: Responses to mTOR Inhibitors and Molecular Analyses

“…Advanced/metastatic thymomas and thymic carcinoma exhibit aggressive behavior[ 4 , 13 ]. They are a distinct clinical entity associated with worse prognosis despite multimodal approach[ 14 ], which underscores the urgent need for the development of novel therapeutic approaches.…”

“…Though several signaling pathways have been explored in thymic tumors, clinical trials with EGFR, KIT, VEGF, and IGF-1R, histone deacetylase, DNA methyltransferase, tropomyosin receptor kinase A, and, cyclin-dependent kinase inhibitors documented only modest clinical responses in advanced disease[ 4 , 5 , 15 ]. Our results show that thymic tumors have diverse molecular abnormalities.…”

“…These observations confirm the complexity of tumor heterogeneity[ 17 ]. Other aberrations included mutations in APC , a tumor suppressor gene often altered in colorectal cancer[ 18 ], or in p53 [ 4 , 19 ]. MCL1 amplification implicated in antiapoptic activity[ 20 ], and loss of CDKN2A/B , a gene that encodes inhibition of cyclin-dependent kinases[ 9 , 21 ] were also seen (Table 2 ).…”

“…Thymic carcinomas are malignant epithelial tumors without the thymus-like features of thymomas[ 3 ]. The molecular pathogenesis of these tumors remains poorly elucidated, although retrospective case studies have demonstrated the presence of rare molecular aberrations in important oncogenes ( EGFR, HER2, KIT, KRAS , and BCL2 ), and tumor suppressor genes ( TP53 , and CDKN2A/B )[ 4 - 9 ].…”

Neoplasias epiteliales del timo: timoma y carcinoma tímico: Caracterización, tratamiento y variables asociadas a supervivencia

“…Un aspecto relevante en el enfrentamiento de las NET, son los significativos avances en biología y patología molecular que recientemente han identificado características moleculares de ellas 6,46,47 . Una caracterización molecular de las NET podría ofrecer estrategias para optimizar el diagnóstico, tratamiento y pronóstico.…”