Complete remission following icotinib administration in an advanced ectopic thymic carcinoma patient harbouring the <i>EGFR</i> exon 19 deletion

Zu, Yun-Fen; Luo, Yan; Li, Chongyang; Zhao, Jiangran; He, Tingting; Shi, Xiaoliang; Li, Xin

doi:10.1002/jgm.3340

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…For example, blockade of EphA2 has been shown to overcome acquired resistance to EGFR kinase inhibitors in lung cancer [36,37]. Although EGFR was by far the most frequently activated RTK in TET in our series, EGFR mutations are very rare [38][39][40], and the efficacy of anti-EGFR drugs appears to be very limited in non-mutated tumors [41]. Thus, studying the interaction of EGFR and Ephrin receptors in TET may merit further investigation.…”

Section: Discussionmentioning

confidence: 85%

Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas

Küffer

Grabowski

Okada

et al. 2022

Cancers

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Background: After initially responding to empiric radio-chemotherapy, most advanced thymomas (TH) and thymic carcinomas (TC) become refractory and require second-line therapy. The multi-target receptor tyrosine kinase (RTK) inhibitor, sunitinib, is one of the few options, especially in patients with thymic carcinomas, and has resulted in partial remissions and prolonged overall survival. However, sunitinib shows variable activity in thymomas, and not all patients benefit equally. A better understanding of its mode of action and the definition of predictive biomarkers would help select patients who profit most. Methods: Six cell lines were treated with sunitinib in vitro. Cell viability was measured by MTS assay and used to define in vitro responders and non-responders. A quantitative real-time assay simultaneously measuring the phosphorylation of 144 tyrosine kinase substrates was used to correlate cell viability with alterations of the phospho-kinome, calculate a sunitinib response index (SRI), and impute upstream tyrosine kinases. Sunitinib was added to protein lysates of 29 malignant TH and TC. Lysates were analyzed with the same phosphorylation assay. The SRI tentatively classified cases into potential clinical responders and non-responders. In addition, the activation patterns of 44 RTKs were studied by phospho-RTK arrays in 37 TH and TC. Results: SRI application separated thymic epithelial tumors (TET) in potential sunitinib responders and resistant cases. Upstream kinase prediction identified multiple RTKs potentially involved in sunitinib response, many of which were subsequently shown to be differentially overexpressed in TH and TC. Among these, TYRO3/Dtk stood out since it was exclusively present in metastatic TH. The function of TYRO3 as a mediator of sunitinib resistance was experimentally validated in vitro. Conclusions: Using indirect and direct phosphoproteomic analyses to predict sunitinib response in malignant TET, we have shown that TH and TC express multiple important sunitinib target RTKs. Among these, TYRO3 was identified as a potent mediator of sunitinib resistance activity, specifically in metastatic TH. TYRO3 may thus be both a novel biomarker of sunitinib resistance and a potential therapeutic target in advanced thymomas and thymic carcinomas.

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Section: Discussionmentioning

confidence: 85%

Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas

Küffer

Grabowski

Okada

et al. 2022

Cancers

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“…Recently, Zu et al presented a patient with advanced TC who harbored an EGFR exon 19 deletion and was treated with icotinib. Eventually, the patient had a complete response for almost 40 months ( 76 ).…”

Section: Targeted Agents In Tetsmentioning

confidence: 99%

Emerging therapies in thymic epithelial tumors (Review)

et al. 2023

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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

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Carboplatin/icotinib/paclitaxel

2021

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Complete remission following icotinib administration in an advanced ectopic thymic carcinoma patient harbouring the EGFR exon 19 deletion

Cited by 4 publications

References 21 publications

Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas

Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas

Emerging therapies in thymic epithelial tumors (Review)

Carboplatin/icotinib/paclitaxel

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