Thymic tumors: relevant molecular data in the clinic

Thymic malignancies are rare intrathoracic tumors that may be aggressive and difficult to treat in advanced stage. Over the past years, significant efforts have been conducted to dissect the molecular pathways involved in the carcinogenesis of these tumors. Insights have been made following anecdotal clinical responses to targeted therapies, and large-scale genomic analyses have been conducted.

Review of the literature, 1990-2010.

The Epidermal Growth Factor Receptor (EGFR) is frequently overexpressed in thymomas and thymic carcinomas, but EGFR mutations are exceptional, and this does not support the use of EGFR tyrosine kinase inhibitors. On the contrary, single observations of responses create a basis for further evaluation of cetuximab in thymomas. KIT-mutant thymic carcinomas represent a small molecular subset of thymic tumors. The clinical relevance of KIT mutations is more limited in thymic carcinoma than in GIST as KIT mutations are far less frequent (7% of thymic carcinomas) and are not correlated with KIT expression; furthermore, KIT mutants are not uniformly sensitive to imatinib. Beyond EGFR and KIT signaling pathways, other molecular alterations with potential prognostic or predictive relevance are emerging in thymic malignancies.

Given the rarity of these tumors, translation of preclinical findings to the clinic may be quick and represents one of the most promising therapeutic approaches for advanced-stage thymic malignancies.