The discovery and development of vandetanib for the treatment of thyroid cancer

Sim, Michael W.; Cohen, Mark S.

doi:10.1517/17460441.2014.866942

Cited by 30 publications

(26 citation statements)

References 39 publications

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“…RET is a well-defined clinical target in thyroid cancer, as recently demonstrated by XL184 and ZD6474, two multikinase inhibitors that are approved for the treatment of advanced MTC [34][35][36][37] . Although AL3810 inhibits RET kinase activity at submicromolar concentrations in enzymatic assays, the high Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer

Xie

Chen

et al. 2017

Acta Pharmacol Sin

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Thyroid cancer is the most common type of endocrine neoplasia. Despite recent breakthroughs in treatment of the disease, the treatment of advanced, progressive thyroid cancers remains challenging with limited therapeutic options available. In this study, we evaluated a novel and orally bioavailable small-molecule multiple tyrosine kinases inhibitor, AL3810, in preclinical models of thyroid cancer in vitro and in vivo. AL3810 (2-5 μmol/L) dose-dependently inhibited the proliferation of human thyroid cancer cell lines TT, SW579 and TPC-1 in vitro with IC values ranging from 0.59 to 7.03 μmol/L. Specifically, this agent dose-dependently arrested the thyroid cancer cells in the G phase and induced apoptosis. Furthermore, AL3810 dose-dependently inhibited the migration and invasion of SW579 and TPC-1 cells in vitro. In SW579 and TT xenograft models, oral administration of AL3810 (5-20 mg·kg·d) for 21 d potently inhibited the tumor growth; immunohistochemical staining revealed that the antitumor activity of AL3810 was closely correlated with its anti-angiogenesis effect, as evidenced by a dose-dependent reduction of microvessels in tumor tissues. To assess the therapeutic potential of AL3810 in treating thyroid cancer involving RET gene fusion, we showed that AL3810 (1-10 μmol/L) dose-dependently inhibited the proliferation of RET-driven Baf3 cell line Baf3-CCDC6-RET, and the auto-phosphorylation of RET in these cells. Our data suggest that AL3810 is a promising agent for the treatment of thyroid cancer.

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Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer

Xie

Chen

et al. 2017

Acta Pharmacol Sin

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“…Thyroid cancer is the most common endocrine malignancy, representing over 90% of all endocrine cancers . Most TCs present as differentiated subtypes, including papillary and follicular carcinomas that respond well to surgery followed by radioactive iodine ablation.…”

Section: Discussionmentioning

confidence: 99%

“…It has inhibitory activity against all EGFRs, except VEGFRs, which are vital to tumor growth and metastasis, as well as having RET inhibitory activity. Vandetanib was first developed as “ZD6474” by Astra‐Zeneca who demonstrated its potent anti‐angiogenesis effects in vitro and in vivo to target and inhibit VEGFR tyrosine kinase . Subsequently, its anti‐tumor effects via the inhibition of EGFR have become apparent.…”

Section: Discussionmentioning

confidence: 99%

New agent to treat advanced or metastasized thyroid cancer, its efficacy, safety, and mechanism

et al. 2015

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BackgroundVandetanib is the first US Food and Drug Administration approved agent to treat advanced or metastasized thyroid cancer. To gain a better understanding of the drug, we conducted a systematic review of its efficacy and safety in patients with thyroid cancers.MethodsTrial data was retrieved from Pubmed, EMBASE, Medline, China National Knowledge Infrastructure, and the Cochrane database without restrictions on language. A systematic review of the literature was performed to assess median progression-free survival (PFS) and adverse events associated with vandetanib therapy for advanced or metastasized thyroid cancers.ResultsVandetanib statistically prolonged PFS in comparison with the placebo (30.5 vs. 19.3 months, hazard ratio 0.46), It even prolonged PFS in surgically unresectable or metastatic differentiated thyroid cancer cases compared with the placebo (11.1 vs. 5.9 months, hazard ratio 0.63). Rash, diarrhea, neutropenia, and hypertension were the most frequent side effects.ConclusionVandetanib can significantly improve PFS. Though it has some side effects, it is still a promising agent in the treatment of advanced or metastasized thyroid cancer, especially in those with metastasized or advanced medullary thyroid carcinoma.

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“…There are at least 11 clinical trials with vandetanib and breast cancer [109][110][111]. It also has undergone clinical trials with epithelial ovarian, fallopian tube or primary peritoneal carcinomas [112], glioblastoma [113], HNSCC [114], NSCLC [115], prostate cancers [116] and thyroid cancers [117,118].…”

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confidence: 99%

“…Significant clinical advances in the past decade have resulted from the development of antibodies and kinase inhibitors that specifically target various EGFR family members.. The targeting of the EGFR family members in various cancer types has been extensively discussed [2,[5][6][7][9][10][11][12][13][14][15]17,18,[20][21][22][23][24][25][27][28][29][30][31][32][33]105,106,108,[110][111][112][113][114][115][116][117][118][119][120][121].…”

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confidence: 99%

Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy

Steelman¹,

Fitzgerald²,

Lertpiriyapong³

et al. 2016

CPD

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The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980's. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses on their roles and other associated pathways in cancer stem cells (CSCs), identifying sites where therapeutic resistance may develop and the mechanisms by which microRNAs (miRs) and other RNAs regulate this pathway. This review will focus on recent advances in these fields with a specific focus on breast cancer and breast CSCs. Relatively novel areas of investigation, such as treatments for other diseases (e.g., diabetes, metabolism, and intestinal parasites), have provided new information about therapeutic resistance and CSCs.

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The discovery and development of vandetanib for the treatment of thyroid cancer

Cited by 30 publications

References 39 publications

Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer

Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer

New agent to treat advanced or metastasized thyroid cancer, its efficacy, safety, and mechanism

Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy

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