Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond

Cabanillas, Maria E.; Ryder, Mabel; Jiménez, Camilo

doi:10.1210/er.2019-00007

Cited by 224 publications

(208 citation statements)

References 177 publications

Supporting

Mentioning

196

Contrasting

Unclassified

Order By: Relevance

“…Although multimodal treatment with surgery, radiation, and chemotherapy is the standard therapy of choice for ATC [2,3,17,18], no effective method has been identified to prevent recurrence. Novel therapeutic agents have been developed to control the systemic or inoperable disease of ATC, including paclitaxel [19], fosbretabulin [20], vascular endothelial growth factor receptor inhibitors: sorafenib [21] and lenvatinib (approved for ATC in Japan only) [22], selective tyrosine kinase inhibitors of V600E mutated BRAF gene: dabrafenib in combination with selective MEK (Mitogen-activated protein kinase/ Extracellular signal related kinase Kinase) inhibitor: trametinib (approved for ATC by the US Food and Drug Administration) [23,24], and immune checkpoint inhibitors [25,26]. In addition, successful neoadjuvant treatment with those agents followed by complete surgical resection as a novel multimodal therapeutic strategy was reported [24].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the 8th Edition TNM Classification for Anaplastic Thyroid Carcinoma

Onoda

Sugitani

Ito

et al. 2020

Cancers

View full text Add to dashboard Cite

Background: The tumor–node–metastasis (TNM) classification system to categorized anaplastic thyroid cancer (ATC) was revised. Methods: The revised system was evaluated using a large database of ATC patients. Results: A total of 757 patients were analyzed. The proportion and median overall survival values (OS: months) for each T category were T1 (n = 8, 1.1%, 12.5), T2 (n = 43, 5.7%, 10.9), T3a (n = 117, 15.5%, 5.7), T3b (n = 438, 57.9%, 3.9), and T4 (n = 151, 19.9%, 5.0). The OS of the N0 and N1 patients were 5.9 and 4.3, respectively (log-rank p < 0.01). Sixty-three (58.3%) patients migrated from stage IV A to IV B by revision based on the existence of nodal involvement and 422 patients (55.7%) were stratified into stage IV B, without a worsening of their OS (6.1), leaving 45 patients (5.9%) in stage IV A with fair OS (15.8). The hazard ratios for the survival of the patients of stage IV B compared to stage IV A increased from 1.1 to 2.1 by the revision. No change was made for stage IV C (n = 290, 38.8%, 2.8). Conclusion: The revised TNM system clearly indicated the prognoses of ATC patients by extracting rare patients with fair prognoses as having stage IV A disease and categorized many heterogeneous patients in stage IV B.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of the 8th Edition TNM Classification for Anaplastic Thyroid Carcinoma

Onoda

Sugitani

Ito

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…332 Cabozantinib, specific for a wide range of TKs, such as MET, RET, and VEGFR-2, is also an FDA-approved drug for metastatic medullary thyroid cancer and renal carcinoma, with antitumor effects in liver cancer, as assessed through phase II and phase III trials. [333][334][335] Similarly, an exciting antitumor performance of cabozantinib was observed in research based on CRC xenograft models and cell lines, while the results from CRC-focused clinical trials are awaited. 289,336,337 Merestinib, an inhibitor of MET, AXL (Axl receptor tyrosine kinase), TEK (tunica interna endothelial cell kinase), ROS1, DDR (discoidin domain receptor tyrosine kinase), MKNK (MAP kinase-interacting serine/threonine protein kinase), and FLT3 (Fms-related tyrosine kinase 3), has just finished its first human phase I trial for various advanced cancers, including CRC, 338 to determine a suitable dose for the phase II trial.…”

Section: The Hgf/c-met Pathwaymentioning

confidence: 99%

Comprehensive review of targeted therapy for colorectal cancer

Xie

Chen

Fang

2020

Sig Transduct Target Ther

1,048

821

View full text Add to dashboard Cite

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents blocking different critical pathways as well as immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide are currently updating the recommended targeted drugs on the basis of the increasing number of high-quality clinical trials. This review provides an overview of existing CRC-targeted agents and their underlying mechanisms, as well as a discussion of their limitations and future trends.

show abstract

“…In recent years, the incidence of DTC has increased [14][15][16][17], with PTC constituting greater than 90% of cases. PTC typically has a good prognosis; however, patients with locally invasive and/or distant metastases have a markedly lower overall survival (OS) rate [18]. The mean OS duration in patients with advanced PTC ranges from less than 6 months to approximately 5 years; therefore, it is imperative that an effective treatment is found.…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative mechanism of Huaier extract in human thyroid carcinoma cells

He¹,

Zhang²,

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundThyroid cancer is the most common endocrine tumor and typically has a good prognosis; however, some patients still present with local or distant metastases. Huaier is a traditional Chinese medicine reported as effective in treating certain types of tumor, but the effect of Huaier on thyroid cancer has not yet been reported. MethodsThe thyroid cancer cell lines, B-CPAP and C643, were treated with increasing concentrations of Huaier extract and the therapeutic effect was measured using a cell counting kit 8 (CCK-8) and flow cytometry. High-throughput sequencing was further performed to identify differentially expressed genes (DEGs) in Huaier-treated B-CPAP cells. Moreover, quantitative real-time PCR (RT-qPCR) was carried out to verify the selected RNAs. Finally, the dual luciferase detection kit was used to detect gene activity.ResultsProliferation of B-CPAP and C643 cells was significantly suppressed by treatment with Huaier extract in a concentration- and time-dependent manner. Huaier extract also induced cell cycle arrest and apoptosis according to flow cytometry (p < 0.05).High-throughput sequencing observed 7,979 significantly altered transcripts. Gene Ontology (GO) analysis showed that 270 genes were enriched in upregulated terms, while 171 genes were enriched in downregulated terms (p < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that there were 47 enriched pathways associated with DEGs (p < 0.05). The expression levels of chosen lncRNAs (SNHG7, MIR181A2HG, ILF3-AS1, and CTA-29F11.1) and their corresponding mRNAs (BBC3, CTSL, GADD45A, and DDIT3) were verified to be overexpressed in Huaier-treated B-CPAP cells by RT-qPCR (p < 0.05).Following transduction, the CCK-8 results showed that the proliferative capacity was increased in the shRNA group as compared with that in the Ctrl and Scr groups. According to flow cytometry, the number of cells in the G0/G1 phase was decreased in the shRNA group (p < 0.01) and the apoptosis rate was lower (p < 0.05). The shRNA-treated group had significantly reduced Huaier-induced apoptosis as compared with the Scr-treated group (p < 0.05). Moreover, the number of cells in the G0/G1 phase in the shRNA-treated group was significantly lower than that in the Scr-treated group (p < 0.05). The results of the dual luciferase reporter gene experiment showed that the activity in the GADD45A WT + miR-301a-3p(+) group was significantly reduced as compared with that in the GADD45A WT + miR-301a-3p(+) NC group (p < 0.01). Further, the activity in the ILF3-AS1 WT + miR-301a-3p(+) group was significantly lower than that in the ILF3-AS1 WT + miR-301a-3p(+) NC group (p < 0.05).ConclusionsThe present study demonstrates that Huaier extract inhibits the proliferation of thyroid cancer cells via changes in the expression levels of a multitude of genes. In particular, a decrease in GADD45A expression enhances the proliferative ability of thyroid cancer cells, the levels of which can be increased by Huaier treatment, thus regulating the cell cycle and apoptosis. Huaier can inhibit the proliferation of thyroid cancer cells through the ILF3-AS1/hsa-miR-301a-3p/GADD45A ceRNA axis.

show abstract

Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond

Cited by 224 publications

References 177 publications

Evaluation of the 8th Edition TNM Classification for Anaplastic Thyroid Carcinoma

Evaluation of the 8th Edition TNM Classification for Anaplastic Thyroid Carcinoma

Comprehensive review of targeted therapy for colorectal cancer

Anti-proliferative mechanism of Huaier extract in human thyroid carcinoma cells

Contact Info

Product

Resources

About