Antineoplastic Activity of CLM29, and CLM3, in Primary Anaplastic Thyroid Cancer Cells (Obtained from Biopsy, or Fine Needle Aspiration)

  • Background Anaplastic thyroid carcinoma (ATC) is an endocrine malignancy, rare but fatal with a mean survival of about 6 months. The median patient survival with the current treatments is of 10 months. Hence, finding new effective treatments for this deadly cancer would be an important progress in the management of this disease. Methods We tested the antiproliferative effect of two new “pyrazolo[3,4-d]pyrimidine” compounds (CLM3, CLM29) in primary cells from ATC (pATC) cultures obtained both from biopsy (biop-pATC), and from fine needle aspiration (FNA-pATC) of 6 patients with ATC. The concentrations used in the in vitro experiments were: 1, 5, 10, 30, 50, 100 mM for CLM3 and 5, 10, 30, 50 mM, for CLM29. Results CLM29 induced a significant reduction of proliferation with respect to the control in both FNA-pATC and  biop-pATC; a slight but significant reduction was obtained also with CLM3. Both compounds led (in a dose-dependent manner) to an increase of the percentage of apoptosis in FNA-pATC, and in biop-pATC. No significant differences were observed about sensitivity to CLM29 or CLM3 between the tested ATC cells from FNA, or biopsy. Discussion & Conclusions We observed that: a) FNA-pATC, and biop-pATC report a similar sensitivity to tyrosine kinase inhibitors; b) both the compounds CLM29 and CLM3 are effective in reducing cell growth and increasing apoptosis in ATC. The opportunity to test the sensitivity to different drugs in each patient could pave the way to personalized treatments, avoiding the administration of inactive therapeutics.

 

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