Multikinase inhibitors in thyroid cancer: timing of targeted therapy

Gild, Matti; Tsang, Venessa; Clifton‐Bligh, Roderick; Robinson, Bruce G.

doi:10.1038/s41574-020-00465-y

Cited by 43 publications

(37 citation statements)

References 104 publications

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“…We recently reported that combination treatment including sorafenib, an MKI, is effective against osteosarcoma in PDOX models, suggesting the potential usefulness of MKIs for treating osteosarcoma (17,18). MKIs prevent progression of many types of cancer by inhibiting multiple hyper-activated-receptor kinases, such as fibroblast-growth-factor receptor, VEGFR, and stem-cell factor (c-KIT) (5,6,8,25). Abnormality of these receptor kinases has also been reported in sarcoma.…”

Section: Discussionmentioning

confidence: 99%

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Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib

Higuchi

Igarashi

Yamamoto

et al. 2021

Cancer Genomics Proteomics

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Background/Aim: Osteosarcoma is a recalcitrant heterogenous malignancy. The aim of the present study was to compare a series of multikinase inhibitors (MKIs) for efficacy on two drug-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) models in order to identify a clinical candidate. Materials and Methods: The two osteosarcoma PDOX models were tested for response to the following MKIs: pazopanib, sunitinib, sorafenib, crizotinib, and regorafenib, in comparison to first-line treatment with cisplatinum and an untreated control. Results: Regorafenib led to regression of osteosarcoma in both PDOXs. Total necrosis was observed pathologically in the regorafenib-treated tumors. Sorafenib arrested growth, without inducing regression, in one osteosarcoma model but not the other, and the other MKIs only slowed tumor growth. Conclusion: The present study demonstrated that regorafenib is much more effective than the other MKIs tested and has clinical potential against recalcitrant osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

“…In recent years, multikinase inhibitors (MKIs) such as sunitinib, sorafenib, pazopanib, crizotinib and regorafenib have shown promising results, initially in renal-cell cancer (RCC) (3), hepatocellular carcinoma (HCC) (4), and thyroid cancer (5). MKIs simultaneously target several kinases (6).…”

mentioning

confidence: 99%

Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib

Higuchi

Igarashi

Yamamoto

et al. 2021

Cancer Genomics Proteomics

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“…As above, there is no strong consensus about when to initiate MKIs for patients with RR-DTC, especially with asymptomatic and progressing disease. Therefore, as a recent review describes, real-world data can assist to optimize the timing of starting MKIs [ 39 ].…”

Section: Recommendation Of Each Guideline For Starting Mkismentioning

confidence: 99%

Clinical Indications for Treatment with Multi-Kinase Inhibitors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer

Fukuda

Takahashi

2021

Cancers

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Differentiated thyroid cancer is usually a slow-growing disease, even if the patients develop distant metastasis. For recurrent or metastatic disease, radioactive iodine therapy is a standard treatment. However, the disease gradually progresses in some of the patients and can ultimately develop into life-threatening conditions. For patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), multi-kinase inhibitors (MKIs) including sorafenib and lenvatinib prolonged progression-free survival compared with placebo in pivotal randomized phase 3 trials, although the benefit in overall survival has not been clearly confirmed, possibly because the patients who received placebo were permitted to cross-over to lenvatinib upon disease progression. Moreover, the adverse events related to MKIs were not negligible. Therefore, the optimal timing of MKI initiation has long been controversial, and physicians should consider various patient and disease factors. Herein, we comprehensively review the clinical factors that can be helpful in determining the initiation of MKIs for patients with RR-DTC.

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“…They inhibit kinases of the vascular endothelial growth factor receptor (VEGFR) 1-3 and of RAF, V-raf murine sarcoma viral oncogene homolog B (BRAF), platelet-derived growth factor receptor (PDGFR), cKIT, FMS-like tyrosine kinase-3 (FLT3), fibroblast growth factor receptor (FGFR) 1-4, and RET for proliferation and normal cell function. GFR signaling acts via the rat sarcoma virus (RAS)/RAF/Mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) cascade (Figure 2) [20]. Binding of a ligand to RTK is the key activation step for the RAS cascade.…”

Section: Thyroid Carcinomamentioning

confidence: 99%

Nanoparticles: Promising Auxiliary Agents for Diagnosis and Therapy of Thyroid Cancers

Frőhlich

Wahl

2021

Cancers

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Cancers of the endocrine system are rare. The majority are not highly malignant tumors. Thyroid cancer (TC) is the most common endocrine cancer, with differentiated papillary and follicular tumors occurring more frequently than the more aggressive poorly differentiated and anaplastic TC. Nanoparticles (NP) (mainly mesoporous silica, gold, carbon, or liposomes) have been developed to improve the detection of biomarkers and routine laboratory parameters (e.g., thyroid stimulating hormone, thyroglobulin, and calcitonin), tumor imaging, and drug delivery in TC. The majority of drug-loaded nanocarriers to be used for treatment was developed for anaplastic tumors because current treatments are suboptimal. Further, doxorubicin, sorafenib, and gemcitabine treatment can be improved by nanotherapy due to decreased adverse effects. Selective delivery of retinoic acid to TC cells might improve the re-differentiation of de-differentiated TC. The use of carbon NPs for the prevention of parathyroid damage during TC surgery does not show a clear benefit. Certain technologies less suitable for the treatment of deeply located cancers may have some potential for unresectable anaplastic carcinomas, namely those based on low-intensity focused ultrasound and near-infrared irradiation. Although some of these approaches yielded promising results in animal studies, results from clinical trials are currently lacking.

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Multikinase inhibitors in thyroid cancer: timing of targeted therapy

Cited by 43 publications

References 104 publications

Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib

Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib

Clinical Indications for Treatment with Multi-Kinase Inhibitors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer

Nanoparticles: Promising Auxiliary Agents for Diagnosis and Therapy of Thyroid Cancers

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