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Do thymic malignancies respond to target therapies?
Bin Hu1, Hao Rong1, Yongtao Han1
1Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Chengdu, China.
Abstract:
A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Do thymic malignancies respond to target therapies?' Altogether, 347 papers were found using the reported search, of which, in our opinion, 16 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. We did not find any randomized controlled trials on target therapies for the thymic malignancies, due to the very small incidence of this tumour, and it seems unlikely that there will be any such trials in the foreseeable future. Three studies on target therapies showed that several cases of thymic malignancies were reported to have partial response (PR) to epidermal growth factor receptor tyrosine kinase inhibitors such as cetuximab and erlotinib, whereas, one study on erlotinib and another on gefitinib showed no activity. Proto-oncogene c-KIT (KIT) mutant thymic carcinomas were noted to benefit from target therapies, implying that systematic sequencing of KIT in thymic carcinoma tumours may be warranted for optimal patient selection. A study that investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody that binds to insulin-like growth factor 1 receptor, indicated that relapsed thymomas tended to respond, whereas thymic carcinoma did not. The antiangiogenesis agent belinostat had modest antitumour activity in heavily pretreated thymoma, but no response to thymic carcinoma was found. Several cases with metastatic thymic carcinoma showed that multitargeted kinase inhibitors, such as sunitinib and sorafenib, were effective. We concluded that, as the side-effects of the agents were tolerable in almost all reported cases, target therapies can be an option for patients with heavily pretreated thymoma.
Insights
Target therapies show potential for thymic malignancies, particularly those with KIT mutations. While randomized trials are lacking, some patients with thymoma and metastatic thymic carcinoma experienced benefits, suggesting these therapies can be an option.
Area of Science:
- Cardiothoracic Surgery
- Oncology
- Molecular Targeted Therapy
Background:
- Thymic malignancies are rare tumors with limited treatment options.
- The efficacy of targeted therapies in thymic malignancies remains largely unexplored due to low incidence.
- Evidence-based review is needed to guide treatment decisions for thymic malignancies.
Purpose of the Study:
- To evaluate the effectiveness of targeted therapies for thymic malignancies.
- To identify specific molecular targets and agents that show promise in treating thymoma and thymic carcinoma.
- To summarize the best available evidence on targeted therapy response in thymic malignancies.
Main Methods:
- Systematic literature search for best evidence on targeted therapies in thymic malignancies.
- Inclusion of 16 high-quality papers from 347 identified articles.
- Tabulation of study characteristics, patient groups, outcomes, and results.
Main Results:
- No randomized controlled trials were found for targeted therapies in thymic malignancies.
- Partial responses observed with epidermal growth factor receptor tyrosine kinase inhibitors (e.g., cetuximab, erlotinib) in some cases.
- Thymic carcinomas with KIT mutations showed benefit from targeted therapies.
- Cixutumumab showed response in relapsed thymomas but not thymic carcinoma.
- Belinostat demonstrated modest activity in pretreated thymoma.
- Multitargeted kinase inhibitors (sunitinib, sorafenib) were effective in metastatic thymic carcinoma.
Conclusions:
- Targeted therapies represent a potential treatment option for heavily pretreated thymoma patients.
- Systematic sequencing for KIT mutations may aid in patient selection for thymic carcinoma.
- Further research is warranted to establish the role of targeted therapies in thymic malignancies.
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