Targeted therapies in advanced differentiated thyroid cancer

Carneiro, R C G; Carneiro, Benedito A.; Agulnik, Mark; Kopp, Peter; Giles, Francis J.

doi:10.1016/j.ctrv.2015.06.002

Cited by 62 publications

(55 citation statements)

References 115 publications

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“…20 Sorafenib has been approved by the US Food and Drug Administration (FDA) for the treatment of hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer. [21][22][23] The anticancer effect of sorafenib for the treatment of CRPC has currently been assessed in Phase II …”

Section: Introductionmentioning

confidence: 99%

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Archibald

Pritchard

Nehoff

et al. 2016

IJN

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Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene- co -maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing.

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Section: Introductionmentioning

confidence: 99%

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Archibald

Pritchard

Nehoff

et al. 2016

IJN

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“…What is clear is that the approval of lenvatinib gives a powerful new option when treating these patients regardless of initial treatment. As multiple other therapies, including RTK inhibitors, BRAF inhibitors, mTOR inhibitors and re-differentiation agents, progress in clinical trials [9] and new, efficacious targeted agents are being developed pre-clinically; patients will have expanded treatment options available in the event of disease progression that may provide additional benefit to the course of their disease.…”

Section: Resultsmentioning

confidence: 99%

The Newest Targeted Therapeutics for Thyroid Cancer: Development of Sorafenib and Lenvatinib

Cohen¹

2016

Chemotherapy (Los Angel)

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Sorafenib was specifically developed using high-throughput screening and structure-activity relationships to target important pathogenic pathways in thyroid cancer. Initially developed to target rapidly accelerated fibrosarcoma (RAF) kinase, it was also found to inhibit several key receptor tyrosine kinases (RTKs) within the mitogen-activated protein kinase (MAPK) pathway. Preclinical and clinical studies demonstrated significant efficacy in differentiated thyroid cancer (DTC), and following the phase III DECISION trial comparing sorafenib to placebo in DTC, it received Food and Drug Administration (FDA) approval in November 2013 for treatment of advanced, radioactive iodine-refractory DTC. Sorafenib is shown to significantly improve progression free survival (PFS) an average of 10.8 months (hazard ratio [HR] 0.59, 95% CI, 0.45-0.76; P<0.0001), although an overall survival (OS) benefit has yet to be proven. An additional targeted RTK inhibitor, lenvatinib, was recently approved by the FDA in February 2015 for advanced, RAIrefractory DTC following the phase III SELECT trial. While lenvatinib has a higher average PFS of 18.3 months (HR 0.21; 99% CI, 0.14-0.31; P<0.001), as well as higher complete and partial response rates, it too has yet to prove an OS benefit. While there is clear evidence of the clinical benefit for both sorafenib and lenvatinib treatment in advanced RAI refractory patients, it is unclear which may be superior. However, each has a different side effect profile that may help guide initial treatment decisions in an individualized approach. Additionally, because lenvatinib demonstrated a similar increase in PFS for those who were previously treated with RTK inhibitors like sorafenib, lenvatinib is a powerful addition to the treatment of advanced DTC and creates another option for either initial therapy or secondary therapy following disease progression.

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“…Although not included in this survey, with increasing knowledge of the molecular pathogenesis of thyroid carcinoma, several targeted therapies are developed for advanced thyroid carcinomas [14].…”

Section: Discussionmentioning

confidence: 99%

“…Multikinase inhibitors (Sorafenib, Lenvatinib, Sunitinib, Pazopanib, Motesanib, Vandetanib, and Cabozantinib), selective BRAF inhibitors (Vemurafenib and dabrafenib), and mTOR inhibitors (Everolimus) are the most promising compounds for patients with advanced thyroid carcinoma [14].…”

Section: Discussionmentioning

confidence: 99%

Changing trends in the management of well-differentiated thyroid carcinoma in Korea

2016

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Targeted therapies in advanced differentiated thyroid cancer

Cited by 62 publications

References 115 publications

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

The Newest Targeted Therapeutics for Thyroid Cancer: Development of Sorafenib and Lenvatinib

Changing trends in the management of well-differentiated thyroid carcinoma in Korea

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