New hopes against anaplastic thyroid carcinoma, one of the most aggressive tumors, currently without treatment and with an average survival of 6 months from diagnosis. An international study coordinated by the University of Santiago de Compostela in Spain, in which Laura Fugazzola, head of the Thyroid Center of the Auxologico San Luca hospital in Milan and professor of endocrinology at the State University of the Lombardy capital, collaborated, has identified a therapeutic agent called PIAS2b-dsRNAi, capable of selectively eliminating anaplastic thyroid cancer cells without any effect on healthy cells. The discovery, published in ‘Nature Communications’, represents “an important step forward in the fight against this serious pathology and, to date, without effective therapy”, explain by UniMi and Auxologico.
Researchers – we read in a note – have characterized for the first time an enzyme called PIAS2b which plays a crucial role in the survival of anaplastic thyroid carcinoma cells. Unlike normal cells and other types of cancer, anaplastic cells depend on PIAS2b for cell division. “This discovery therefore led to the possibility of designing a therapy aimed at directly counteracting the activity of this key enzyme,” Fugazzola reports. “It is – he specifies – a therapeutic agent based on a double-stranded RNA, transcribed in vitro, called “PIAS2b-dsRNAi”, which is capable of silencing the enzyme in anaplastic cells. Consequently the cells lose their ability to divide and die through a process called mitotic catastrophe”.
The efficacy of PIAS2b-dsRNAi was evaluated using primary cultures of anaplastic cancer cells, compared with cells from healthy tissues or from benign thyroid disease or other types of thyroid cancer. The results demonstrated that the therapeutic agent is highly selective and acts only on anaplastic cells. Preclinical in vivo studies were then performed, implanting anaplastic carcinomas of patients into mouse models, with tumor growth blocked after the administration of PIAS2b-dsRNAi. “An extremely interesting fact – underlines Fugazzola – is that PIAS2b-dsRNAi has proven effective in eliminating anaplastic cells with other localizations, including pancreas and lung. This versatility opens the door to broader applications in the treatment of different types of anaplastic carcinoma , for which therapeutic possibilities are currently extremely limited”. The researchers’ hope is that “pharmaceutical companies can contribute to the clinical development of this compound to get it to patients as soon as possible”.
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