Management of VEGFR-Targeted TKI for Thyroid Cancer

Enokida, Tomohiro; Tahara, Makoto

doi:10.3390/cancers13215536

Cited by 21 publications

(10 citation statements)

References 118 publications

(188 reference statements)

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“…In fact, TKIs exert immunomodulatory properties that may shift the tumor microenvironment from immunosuppressive to immune-permissive [ 28 ]. However, different life-threatening off-target toxicities have been described, including thyroid dysfunctions, cardiovascular events, bleeding, proteinuria/renal impairment, hepatotoxicity, gastrointestinal perforations, metabolic and wound healing complications with an impact on quality of life and monitoring strategies [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System

Raschi

Fusaroli

Giunchi

et al. 2022

Cancers

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Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January 2004–March 2022) were identified through the high-level term “adrenal cortical hypofunctions”. Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs). Results: Out of 147,153 reports with VEGFR-TKIs, 314 cases of AI were retained, mostly of which were serious (97.1%; hospitalization recorded in 44.9%). In a combination regimen with ICIs (43% of cases), VEGFR-TKIs were discontinued in 52.2% of the cases (26% as monotherapy). The median time to onset was 72 days (IQR = 14–201; calculated for 189 cases). A robust disproportionality signal emerged, also in comparison with other anticancer drugs (ROR = 2.71, 95%CI = 2.42–3.04; IC = 0.25, 95%CI = 0.07–0.39). Cabozantinib, sunitinib and axitinib generated robust disproportionality even after ROR adjustment. Conclusions: We call pharmacologists, internists, oncologists and endocrinologists to raise awareness of serious AI with VEGFR-TKIs, and to develop dedicated guidelines, especially for combination regimens with immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System

Raschi

Fusaroli

Giunchi

et al. 2022

Cancers

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“…Angiogenesis is affected by vascular endothelial growth factor (VEGF), and studies have shown that the expression of VEGF gene is upregulated in thyroid cancer, especially in ATC. Tyrosine kinase inhibitors of VEGF receptors are currently used as targeted therapies for ATC patients [ 43 , 45 , 46 ]. The treatment of ATC cell lines with BI-847325 may decrease tumor angiogenesis by reducing VEGF expression (Fig.…”

Section: Discussionmentioning

confidence: 99%

BI-847325, a selective dual MEK and Aurora kinases inhibitor, reduces aggressive behavior of anaplastic thyroid carcinoma on an in vitro three-dimensional culture

et al. 2022

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Background Anaplastic thyroid carcinoma (ATC) is the most aggressive subtype of thyroid cancer. In this study, we used a three-dimensional in vitro system to evaluate the effect of a dual MEK/Aurora kinase inhibitor, BI-847325 anticancer drug, on several cellular and molecular processes involved in cancer progression. Methods Human ATC cell lines, C643 and SW1736, were grown in alginate hydrogel and treated with IC50 values of BI-847325. The effect of BI-847325 on inhibition of kinases function of MEK1/2 and Aurora kinase B (AURKB) was evaluated via Western blot analysis of phospho-ERK1/2 and phospho-Histone H3 levels. Sodium/iodide symporter (NIS) and thyroglobulin (Tg), as two thyroid-specific differentiation markers, were measured by qRT-PCR as well as flow cytometry and immunoradiometric assay. Apoptosis was assessed by Annexin V/PI flow cytometry and BIM, NFκB1, and NFκB2 expressions. Cell cycle distribution and proliferation were determined via P16, AURKA, and AURKB expressions as well as PI and CFSE flow cytometry assays. Multidrug resistance was evaluated by examining the expression of MDR1 and MRP1. Angiogenesis and invasion were investigated by VEGF expression and F-actin labeling with Alexa Fluor 549 Phalloidin. Results Western blot results showed that BI-847325 inhibits MEK1/2 and AURKB functions by decreasing phospho-ERK1/2 and phospho-Histone H3 levels. BI-847325 induced thyroid differentiation markers and apoptosis in ATC cell lines. Inversely, BI-847325 intervention decreased multidrug resistance, cell cycle progression, proliferation, angiogenesis, and invasion at the molecular and/or cellular levels. Conclusion The results of the present study suggest that BI-857,325 might be an effective multi-targeted anticancer drug for ATC treatment.

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“…Thyroid cancer aggressiveness is associated with increased angiogenesis and the expression of VEGF/VEGFR, PDGF/PDGFR, and EGF/EGFR [43,44]. In differentiated thyroid cancer, VEGFR and VEGFR-2 are overexpressed and contribute to tumor progression and aggressiveness.…”

Section: Vegfmentioning

confidence: 99%

Thyroid Cancer: From Genes to Treatment – Recent Developments

Kostoglou-Athanassiou¹

2023

Thyroid Cancer - The Road From Genes to Successful Treatment

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Thyroid cancer carries a good prognosis in most cases and is treated by thyroidectomy, radioiodine administration thereafter, thyroxine treatment. Although, most cases of thyroid cancer are curable, if thyroid cancer loses the ability to concentrate iodine and thus becomes refractory to radioiodine, and if thyroid cancer becomes a progressive disease, the need for targeted treatment becomes necessary. Research in the area of the biology of thyroid cancer and in particular the discovery of somatic genetic mutations involved in the pathophysiology of thyroid cancer as well as research in the treatment of other cancer types with tyrosine kinase inhibitors have led to the application of tyrosine kinase and angiogenetic factor inhibitors in the treatment of thyroid cancer. The application of tyrosine kinase inhibitors in other tumor types led to the discovery that they target the thyroid. Thus, tyrosine kinase inhibitors entered the field of radioactive iodine refractory and advanced thyroid cancer treatment. Multi-kinase and angiogenetic factor inhibitors have provided a novel method that targets thyroid tumors and have revolutionized the treatment of radioiodine refractory and advanced thyroid cancer.

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Management of VEGFR-Targeted TKI for Thyroid Cancer

Cited by 21 publications

References 118 publications

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System

BI-847325, a selective dual MEK and Aurora kinases inhibitor, reduces aggressive behavior of anaplastic thyroid carcinoma on an in vitro three-dimensional culture

Thyroid Cancer: From Genes to Treatment – Recent Developments

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