TY - JOUR T1 - New Imidazo[2,1-<em>b</em>][1,3,4]Thiadiazole Derivatives Inhibit FAK Phosphorylation and Potentiate the Antiproliferative Effects of Gemcitabine Through Modulation of the Human Equilibrative Nucleoside Transporter-1 in Peritoneal Mesothelioma JF - Anticancer Research JO - Anticancer Res SP - 4913 LP - 4919 DO - 10.21873/anticanres.14494 VL - 40 IS - 9 AU - GIOVANNA LI PETRI AU - CAMILLA PECORARO AU - ORNELLA RANDAZZO AU - SILVIA ZOPPI AU - STELLA MARIA CASCIOFERRO AU - BARBARA PARRINO AU - DANIELA CARBONE AU - BTISSAME EL HASSOUNI AU - ANDREA CAVAZZONI AU - NADIA ZAFFARONI AU - GIROLAMO CIRRINCIONE AU - PATRIZIA DIANA AU - GODEFRIDUS J. PETERS AU - ELISA GIOVANNETTI Y1 - 2020/09/01 UR - http://ar.iiarjournals.org/content/40/9/4913.abstract N2 - Background/Aim: A new class of imidazo[2,1-b][1,3,4]thiadiazole compounds have recently been evaluated as inhibitors of phosphorylation of focal adhesion kinase (FAK) in pancreatic cancer. FAK is overexpressed in mesothelioma and has recently emerged as an interesting target for the treatment of this disease. Materials and Methods: Ten imidazo[2,1-b][1,3,4]thiadiazole compounds characterized by indole bicycle and a thiophene ring, were evaluated for their cytotoxic activity in two primary cell cultures of peritoneal mesothelioma, MesoII and STO cells. Results: Compounds 1a and 1b showed promising antitumor activity with IC50 values in the range of 0.59 to 2.81 μM in both cell lines growing as monolayers or as spheroids. Their antiproliferative and antimigratory activity was associated with inhibition of phospho-FAK, as detected by a specific ELISA assay in STO cells. Interestingly, these compounds potentiated the antiproliferative activity of gemcitabine, and these results might be explained by the increase in the mRNA expression of the key gemcitabine transporter human equilibrative nucleoside transporter-1 (hENT-1). Conclusion: These promising results support further studies on new imidazo[2,1-b][1,3,4]thiadiazole compounds as well as on the role of both FAK and hENT-1 modulation in order to develop new drug combinations for peritoneal mesothelioma. ER -