CLM94, a Novel Cyclic Amide with Anti-VEGFR-2 and Antiangiogenic Properties, Is Active against Primary Anaplastic Thyroid Cancer in Vitro and in Vivo

Antonelli, Alessandro; Bocci, Guido; Motta, Concettina La; Ferrari, Silvia; Fallahi, Poupak; Ruffilli, Ilaria; Domenicantonio, Andrea Di; Fioravanti, Anna; Sartini, Stefania; Minuto, Michele; Piaggi, Simona; Corti, Alessandro; Alì, Greta; Desidero, Teresa Di; Berti, Piero; Fontanini, Gabriella; Danesi, Romano; Settimo, Federico Da; Miccoli, Paolo

doi:10.1210/jc.2011-1987

Cited by 51 publications

(45 citation statements)

References 35 publications

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“…However other prospective studies are needed to identify more accurate molecular markers. Finally the knowledge of these molecular pathways has permitted the development of new targeted therapies for aggressive thyroid cancer [83, 84]. …”

Section: Resultsmentioning

confidence: 99%

Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules

Fallahi

Giannini

Miccoli

et al. 2014

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“The incidence of thyroid cancer, the most common endocrine malignancy, is rising. The two most common types of thyroid cancer are papillary and follicular” thyroid carcinomas. “Fine-needle aspiration (FNA) of thyroid nodules” can permit to detect many genetic mutations and other molecular alterations, including RAS and BRAF point mutations, PAX8/peroxisome proliferator-activated receptor (PPAR)γ and “RET/PTC rearrangements, occurring in thyroid papillary and follicular carcinomas” (more than 70% of cases), which can be used successfully to improve the diagnosis “and the management of patients with thyroid nodules”. The most extensive experience has been accumulated with “the diagnostic use of BRAF mutation”, which is highly specific for malignancy. “Testing FNA samples for a panel of mutations” that typically includes RAS, BRAF, PAX8/PPARγ and RET/PTC could permit to achieve the biggest diagnostic impact. “The accuracy of cancer diagnosis in thyroid nodules could be improved significantly using these and other emerging molecular markers”.

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Section: Resultsmentioning

confidence: 99%

Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules

Fallahi

Giannini

Miccoli

et al. 2014

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“…The possibility to test the sensitivity of primary TC cells from each subject to sorafenib, or other different TKIs, might ameliorate the effectiveness of the treatment [87,88].…”

Section: Limits and Drug Resistancementioning

confidence: 99%

Sorafenib in the treatment of thyroid cancer

Ferrari

Politti

Spisni

et al. 2015

Expert Review of Anticancer Therapy

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Sorafenib has been evaluated in several Phase II and III studies in patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid carcinomas (DTCs), reporting partial responses, stabilization of the disease and improvement of progression-free survival. Best responses were observed in lung metastases and minimal responses in bone lesions. On the basis of these studies, sorafenib was approved for the treatment of metastatic DTC in November 2013. Few studies suggested that reduction of thyroglobulin levels, or of average standardized uptake value at the fluorodeoxyglucose-PET, could be helpful for the identification of responding patients; but further studies are needed to confirm these results. Tumor genetic marker levels did not have any prognostic or predictive role in DTC patients.The most common adverse events observed included skin toxicity and gastrointestinal and constitutional symptoms. Encouraging results have also been observed in patients with medullary thyroid cancer. Many studies are ongoing to evaluate the long-term efficacy and tolerability of sorafenib in DTC patients.

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“…Recently, Antonelli et al have shown the anti-tumoral activity of a novel cyclic amide, CLM94, with VEGFR-2 and anti-angiogenic activity, in primary ATC cells (ANA) both in vitro and in vivo [94]. …”

Section: Vegf Pathwaymentioning

confidence: 99%

“…For the above mentioned reasons, the identification of new active compounds against aggressive DTC is needed [94, 95]. …”

Section: Resistance To Targeted Therapiesmentioning

confidence: 99%

Personalization of Targeted Therapy in Advanced Thyroid Cancer

Fallahi

Ferrari

Mazzi

et al. 2014

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Although generally the prognosis of differentiated thyroid carcinoma (DTC) is good, approximately 5% of people are likely to develop metastases which fail to respond to radioactive iodine, and other traditional therapies, exhibiting a more aggressive behavior. Nowadays, therapy is chosen and implemented on a watch-and-wait basis for most DTC patients. Which regimen is likely to work best is decided on the basis of an individual’s clinical information, but only data referring to outcomes of groups of patients are employed. To predict the best course of therapy, an individual patient’s biologic data is rarely employed in a systematic way. Anyway, the use of not expensive individual genomic analysis could lead us to a new era of patient-specific and personalized care. Recently, key targets that are now being evaluated in the clinical setting have been evidenced in the pathogenesis of these diseases. Some of the known genetic alterations playing a crucial role in the development of thyroid cancer include B-Raf gene mutations, rearranged during transfection/ papillary thyroid carcinoma gene rearrangements, and vascular endothelial growth factor receptor-2 angiogenesis pathways. The development of targeted novel compounds able to induce clinical responses and stabilization of disease has overcome the lack of effective therapies for DTC, which are resistant to radioiodine and thyroid stimulating hormone-suppressive therapy. Interestingly, the best responses have been demonstrated in patients treated with anti-angiogenic inhibitors such as vandetanib and XL184 in medullary thyroid cancer, and sorafenib in papillary and follicular DTC.

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CLM94, a Novel Cyclic Amide with Anti-VEGFR-2 and Antiangiogenic Properties, Is Active against Primary Anaplastic Thyroid Cancer in Vitro and in Vivo

Abstract: The antitumor and antiangiogenic activity of a new "cyclic amide" compound, CLM94, is very promising in ATC, opening the way to a future clinical evaluation.

Cited by 51 publications

References 35 publications

Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules

Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules

Sorafenib in the treatment of thyroid cancer

Personalization of Targeted Therapy in Advanced Thyroid Cancer

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