Differentiated Thyroid Cancer: Focus on Emerging Treatments for Radioactive Iodine-Refractory Patients

Gruber, Joshua J.; Colevas, A. Dimitrios

doi:10.1634/theoncologist.2014-0313

Cited by 64 publications

(56 citation statements)

References 85 publications

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“…They achieved clinical benefits in terms of partial response of 12.5-38%, progression-free survival from 9 to 24 months in radioiodine-refractory DTC metastases [37,91]. The therapeutic effects of other tyrosine kinase inhibitors including sunitinib, imatinib, vandetanib were also summarized [37] and a dozen ongoing trials currently listed in the ClinicalTrials.gov database, evaluating 12 kinase-inhibiting drugs [93].…”

Section: Multi-targeted Kinase Inhibitorsmentioning

confidence: 99%

Differentiated Thyroid Carcinoma with Elevated Thyroglobulin and Negative Radioiodine Whole-Body Scan Metastases

Ma¹

2016

Thyroid Cancer - Advances in Diagnosis and Therapy

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Serum thyroglobulin Tg and Tg antibody Tg"b levels, together with neck ultrasonography and I whole-body scintigraphy W"S , are diagnostic tools for postoperative follow-up of patients with differentiated thyroid carcinoma DTC . Generally, good correlation is seen between Tg and W"S in follow-up studies for DTC after thyroid remnant ablation. Undetectable serum Tg with negative W"S results suggests complete remission, whereas detectable, or elevated, serum Tg is associated with radioiodine uptake in local or distant metastases. Patients with thyroid cancer cells lacking radioiodine uptake despite an elevated serum Tg level have been referred to as W"S-negative, Tg-positive patients, who represent % of cases. F-FDG PET FDG-PET scanning should be considered in high-risk DTC patients with negative W"S and positive Tg. The preferred therapeutic hierarchy for Tg-positive and W"Snegative metastases is surgical excision of loco-regional disease, I therapy for radioiodine-responsive disease, external beam radiation, TSH suppression, and systemic therapy with kinase inhibitors. If FDG-PET diagnostic results are negative, one course of I treatment may be considered in high-risk patients and individualized. No further I therapy is indicated for patients with a negative post-therapy W"S.

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Section: Multi-targeted Kinase Inhibitorsmentioning

confidence: 99%

Differentiated Thyroid Carcinoma with Elevated Thyroglobulin and Negative Radioiodine Whole-Body Scan Metastases

Ma¹

2016

Thyroid Cancer - Advances in Diagnosis and Therapy

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“…In the last decade, several studies have evaluated a possible use of axitinib, lenvatinib, motesanib, pazopanib, sorafenib, sunitinib, cabozantinib and vandetanib alone or in association, in aggressive DTC or MTC, but only a few have been approved [50,88,89].…”

Section: Tkismentioning

confidence: 99%

Cabozantinib in Thyroid Cancer

Fallahi¹,

Ferrari²,

Bari³

et al. 2015

PRA

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Cabozantinib is an oral once-daily multitarget tyrosine kinase inhibitor of MET, VEGFR2, RET, acting against KIT, AXL, FLT3 and Tie-2. Cabozantinib has shown anti-cancer effects in preclinical and clinical models of cancers derived from both epithelial and mesenchymal origins [prostate cancer, non small lung cancer, medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC), renal cell carcinoma, etc.]. In a Phase III clinical study, cabozantinib improved PFS (11.2 months versus 4.0 months in the placebo group) of patients with MTC (independently of age, bone metastases, RET status and prior treatment). Cabozantinib was approved in 2012 by FDA for metastatic MTC and in 2013 by EMA. Cabozantinib has been also evaluated in metastatic DTC patients, because they have activation on tyrosine kinases, including MET, VEGFR2 and RET, suggesting the possible use of cabozantinib in metastatic DTC. Actually, two Phase II trials of cabozantinib in DTC patients resistant to RAI are ongoing. To increase the antineoplastic effect of cabozantinib, and to overcome the occurrence of drug resistance, combination studies with other anticancer agents are ongoing. In conclusion, cabozantinib has shown to exert an important therapeutic effect in patients with MTC improving PFS. In DTC patients, cabozantinib has shown promising results.

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“…[5][6][7] In addition, some patients exhibit degenerative changes in tumor cells and function during the disease course, reducing the benefits conferred by 131 I treatment. 8,9 Therefore, a non-invasive, specific diagnostic method combined with an effective molecular marker for targeted therapy is required for PTC.…”

Section: Introductionmentioning

confidence: 99%

<p>Preparation and SPECT/CT Imaging of <sup>177</sup>Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice</p>

Li¹,

Zhang²,

Li³

et al. 2020

OTT

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The expression of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxyterminal domain 1 (CITED1) is upregulated in papillary thyroid carcinoma (PTC) and mediates cell proliferation and migration. To facilitate early diagnosis and monitoring of recurrent or metastatic PTC, we designed 177 Lu-labeled antisense peptide nucleic acid (PNA) targeting CITED1 mRNA to evaluate the therapeutic potential, while analyzing its distribution in nude mice and the characteristics withsingle-photon emission-computed tomography/ computed tomography (SPECT/CT) imaging. Materials and Methods: 177 Lu-DOTA-anti-CITED1-PNA (177 Lu-asPNA) was obtained by indirect labeling. High-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were used to determine the labeling rate and radiochemical purity. The stability of 177 Lu-asPNA was evaluated by TLC, and the radioactivity count was measured by a γ counter to calculate its uptake capacity in K1 cells. To analyze the distribution of 177 Lu-asPNA in body tissues and organs of nude mice, static single-photon emission-computed tomography (SPECT) imaging and SPECT/CT image fusion were performed. Then, the therapeutic effects of probes were explored by tumor growth curves and survival analysis. Results: Our probe showed a radiochemical purity of 96.5±0.15% at 1 hr and specific activity of 8.7±0.53 MBq/μg. The uptake rate in the 177 Lu-asPNA group was much higher than that in the 177 Lu-DOTA-nonsense-PNA (177 Lu-nonsense-PNA) and 177 Lu-DOTA groups (P<0.05). The biological distribution showed that the tumor/muscle ratio was at its highest at 24 h (4.98±0.34) post-inoculation, with SPECT/CT imaging showing clear tumor development. By measuring tumor volume of tumor-bearing nude mice, the 177 Lu-asPNA group showed a significant difference in tumor size 9 days after injection (P < 0.05). Kaplan-Meier survival curves showed that the overall survival rate in the 177 Lu-asPNA group was significantly different from those in the DOTA-anti-CITED1-PNA (asPNA) and saline groups (P = 0.002, log-rank test). Conclusion: 177 Lu-asPNA was developed successfully, showing a high labeling rate and good stability. SPECT/CT imaging demonstrated tumor growth in nude mice, which was effectively inhibited by our probe, thus prolonging survival.

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Differentiated Thyroid Cancer: Focus on Emerging Treatments for Radioactive Iodine-Refractory Patients

Cited by 64 publications

References 85 publications

Differentiated Thyroid Carcinoma with Elevated Thyroglobulin and Negative Radioiodine Whole-Body Scan Metastases

Differentiated Thyroid Carcinoma with Elevated Thyroglobulin and Negative Radioiodine Whole-Body Scan Metastases

Cabozantinib in Thyroid Cancer

<p>Preparation and SPECT/CT Imaging of <sup>177</sup>Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice</p>

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