RNAi, una nueva estrategia terapéutica en Carcinoma Anaplásico de Tiroides

Abstract

Anaplastic thyroid carcinoma (ATC) has a low incidence but is lethal, with rare cases of survival for more than a few months. There are no specific clinical trials nor effective therapies. Our group has established a system where thyroid cancer from patients is cultivated in a standardized way parallelly with their benign/normal samples in order to study specific differences from the cancer. Through differential proteomics between cancer and benign samples, a PIAS2 protein more expressed in thyroid cancer was discovered. An RNA interference (dsRNAi) specific for beta isoform was designed. PIAS2b dsRNAi induces death of anaplastic cells without affecting differentiated carcinoma cells. Through cellular and molecular biology techniques and an in vivo orthotopic PDX model it was demonstrated that PIAS2 is essential for the mitosis of the anaplastic cells and their reduction induces mitotic catastrophe. PIAS2b is a specific therapeutic target in ATC.