EFFECT OF VALPROIC ACID ON INCREASING RADIOSENSITIVITY IN ANAPLASTIC THYROID CANCER CELLS

PERONA, MARINA; IBAÑEZ IL; ROSEMBLIT C; GRISSI C; CREMASCHI GA; PISAREV, MARIO A.; DURAN H; JUVENAL GJ

Mar del Plata

Congreso; Reunion Conjunta SAIC, SAFE, SAB, SAP; 2019

Anaplastic thyroid cancer (ATC) is one of the most lethal solid tumors and it usually has a rapidly fatal clinical course, its median survival being less than 5 months from diagnosis. Although rare (2% of all thyroid cancers), ATC accounts for 14?50% of total mortality for thyroid cancer. In the last decade, multimodality treatment (surgery if feasible, followed by radiotherapy in combination with various chemotherapeutic drugs) has been recommended as the optimal approach, but the results of such treatment still remain poor without significant impact on the survival rates and important side effects (1). Histone deacetylase inhibitors (HDACI) represent a class of therapeutic agents with broad activity against cancer cells, namely, cytotoxic effects, induction of cell differentiation, and synergism with established and experimental cancer therapeutics (2). In preclinical studies, the combination therapy of HDACI with chemotherapeutic agents enhanced drug therapeutic efficacy against ATC (3). Micro-RNAs (miRs) are endogenous small non-coding RNA of about 19 to 22 nucleotides that modulate gene expression through translational repression, or degradation of the target messenger RNA (mRNA) (4). HDACi treatment could modulate miR expression in tumor cells (5). The identification of IR- and HDACI-induced changes in miR expression and their impact on the radiation response, as well as the characterization of potential targets that sensitize tumor cells to IR, could represent an alternative approach for the treatment of ATC.