Emerging therapies in thymic epithelial tumors (Review)

Abstract

Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare malignancies arising from the thymus gland. The optimal management requires a multidisciplinary approach. Standard first-line systemic treatment involves cytotoxic chemotherapeutic regimens; however, alternative options for systemic treatment are required. Current research focuses on the unique profile of immune-related pathogenic mechanisms of TETs, involving an overlap with certain autoimmune phenotypes, as well as on determining the landscape of oncogenic molecular alterations and the role of tumor angiogenesis. The aim of the present review is to summarize the current clinical investigation on immunotherapy and targeted agents in the management of TETs. Regarding immune checkpoint inhibitors, efficacy results are promising in certain subsets of patients; however, caution is required concerning their toxicity. Anti-angiogenic agents, mainly potent small-molecule inhibitors, have demonstrated antitumor activity in TETs, whereas other targeted agents, including KIT inhibitors and epigenetic agents, are associated with encouraging, yet still modest results for unselected populations, in the absence of predictive biomarkers. Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types. Contents 1. Introduction 2. Immunotherapy in TETs 3. Targeted agents in TETs 4. Discussion 5. Conclusions

PD-L1 Expression in Neoplastic and Immune Cells of Thymic Epithelial Tumors: Correlations with Disease Characteristics and HDAC Expression

“…Different PD-L1 expression levels, ranging from 1% to 50%, have been set as cut-offs for administering ICIs in different tumors [13]. For the case of TETs, phase I/II clinical trials assess the safety and efficacy of PD-1/PD-L1 inhibitors, namely, pembrolizumab, nivolumab, atezolizumab, and avelumab (reviewed in [14,15]), with pembrolizumab demonstrating encouraging results in the setting of relapsed and refractory cases [16,17]. The crucial role of PD-L1 expression profile as a distinctive factor between responders and non-responders to immunotherapy means that a better understanding of the molecular networks, especially the epigenetic programs governing PD-L1 transcription levels, could help identify novel candidate pathways of therapeutic intervention, which could be targeted in the setting of combination regimens to enhance the efficacy of immunotherapy.…”

Differences and similarities of GTF2I mutated thymomas in different Eurasian ethnic groups

“…The therapeutic options in thymomas are limited ( 15 ). While many glandular tumors are attributable to targeted therapies ( 16 , 17 ), to date no GTF2I specific drug is available.…”