Novel Biologic Therapies for Thymic Epithelial Tumors

Chen, Yuanbin; Gharwan, Helen; Thomas, Anish

doi:10.3389/fonc.2014.00103

Cited by 10 publications

(10 citation statements)

References 21 publications

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“…Nevertheless, these efforts have helped identify unique molecular changes in TETs such as an anti-apoptotic gene signature and mutations in genes involved in histone modification, DNA methylation and chromatin remodeling in thymic carcinomas (Bellissimo et al, 2017; Huang et al, 2013; Petrini et al, 2013; Wang et al, 2014). Despite these discoveries, attempts to use molecular-targeted agents for treatment of TETs have met with limited success thus far (Chen et al., 2014). Herein, we present a multi-platform, comprehensive analysis of TETs as part of The Cancer Genome Atlas (TCGA) Project to uncover the integrated genomic landscape of these rare tumors.…”

Section: Introductionmentioning

confidence: 99%

The Integrated Genomic Landscape of Thymic Epithelial Tumors

et al. 2018

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Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.

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Section: Introductionmentioning

confidence: 99%

The Integrated Genomic Landscape of Thymic Epithelial Tumors

et al. 2018

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“…However, treatment options for relapsed or refractory disease are limited (5). Targeted therapies, such as epidermal growth factor receptor inhibitors (gefitinib, erlotinib with bevacizumab, cetuximab), angiogenesis inhibitors (sunitinib and aflibercept), c-KIT pathway inhibitors (imatinib), histone deacetylase inhibitors (belinostat), octreotide, and Src inhibitors (saracatinib), among others, have been evaluated in relapsed and refractory TETs, but have shown modest and short-lived responses (6–9).…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors for treatment of thymic epithelial tumors: how to maximize benefit and optimize risk?

Zhao

Rajan

2019

Mediastinum

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A greater understanding of anti-tumor immunity has resulted in rapid development of immunotherapy for a wide variety of cancers. Antibodies targeting the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death-1 (PD-1), or its ligand (PD-L1) have demonstrated clinical activity and are approved for treatment of melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, bladder cancer, head and neck cancers, esophageal cancer, hepatocellular carcinoma, and Hodgkin lymphoma, among others. Treatment is generally well tolerated with relatively few adverse events compared with standard treatments such as chemotherapy. However, immune activation can potentially affect any organ system and a small fraction of patients are at risk for developing severe immunerelated adverse events. Immune checkpoint inhibitors (ICIs) and other immunotherapeutic modalities such as cancer vaccines are in nascent stages of development for treatment of thymic epithelial tumors (TETs). Since the thymus plays a key role in the development of immune tolerance, thymic tumors have a unique biology which can influence the risk-benefit balance of immunotherapy. Indeed, early results from clinical trials have demonstrated clinical activity, albeit at a cost of a higher incidence of immune-related adverse events, which seem to particularly affect skeletal and cardiac muscle and the neuromuscular junction. In this paper we describe the effects of thymic physiology on the immune system and review the results of clinical trials that have evaluated immunotherapy for treatment of relapsed thymoma and thymic carcinoma. We review ongoing efforts to mitigate the risk of immune-related complications in patients with TETs receiving immunotherapy and offer our thoughts for making immunotherapy a feasible alternative for treatment of thymic tumors.

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“…Chemotherapy is associated with objective response rates (ORR) of 50–90% in the front-line setting, but limited benefit is observed in patients with recurrent disease (1,2). With few exceptions, biological agents have not demonstrated clinically meaningful activity in relapsed or refractory TETs (3). A low tumor mutation burden and paucity of actionable biological targets creates challenges for the development of targeted therapies for TETs (4,5).…”

mentioning

confidence: 99%

WT1 as an immunotherapy target for thymic epithelial tumors: a novel method to activate anti-tumor immunity

Takahashi¹,

Zhao²,

Rajan³

2019

Mediastinum

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Thymic epithelial tumors (TETs) are a family of rare cancers that exhibit diverse histology and variable clinical behavior (1). A significant fraction of patients, especially those with thymic carcinoma, have locally-advanced or metastatic disease at diagnosis that is often unresectable (1). Chemotherapy is associated with objective response rates (ORR) of 50-90% in the front-line setting, but limited benefit is observed in patients with recurrent disease (1,2). With few exceptions, biological agents have not demonstrated clinically meaningful activity in relapsed or refractory TETs (3). A low tumor mutation burden and paucity of actionable biological targets creates challenges for the development of targeted therapies for TETs (4,5). Hence, there is a pressing need to develop new treatments, especially for patients with advanced thymic carcinomas.

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Novel Biologic Therapies for Thymic Epithelial Tumors

Cited by 10 publications

References 21 publications

The Integrated Genomic Landscape of Thymic Epithelial Tumors

The Integrated Genomic Landscape of Thymic Epithelial Tumors

Immune checkpoint inhibitors for treatment of thymic epithelial tumors: how to maximize benefit and optimize risk?

WT1 as an immunotherapy target for thymic epithelial tumors: a novel method to activate anti-tumor immunity

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