Evolving treatment landscape in thymic epithelial tumors: From mechanism to therapy

Thymic epithelial tumors (TETs) are rare neoplasms of the anterior mediastinum that arise from thymic epithelial cells. Although surgery is the preferred treatment for resectable TETs, the options for unresectable or recurrent advanced-stage TETs are limited beyond platinum-based chemotherapy. The evolving landscape of TET treatments is marked by significant advancements in targeted therapies and immunotherapies, particularly with anti-angiogenic agents and immune checkpoint inhibitors (ICIs). While monotherapies demonstrated certain efficacy, the development of combination strategies is vital for improving patient outcomes. This review consolidates progress in anti-angiogenic therapies and ICIs, emphasizing the evolution of combination therapies of TETs. Furtherly, we particularly discuss new first-line strategies based on these advancements and emphasizes exploring novel treatments like antibody-drug conjugates, immunomodulatory drugs and cytokine-based agents for TETs. Mechanistically, the molecular features of TETs integrated with clinical diagnosis and targeted therapy, and immunophenotyping of TETs along with its impact on the efficacy and safety of immunotherapy are discussed. Thus, this review systemizes the development in the treatment landscape of TETs, integrating the corresponding molecular and immune mechanisms, aiming to provide new references for the treatment of TETs.