Pivaloyl-substituted 2-pyrrolones induce death of gastrointestinal stromal tumors resistant to imatinib and chemotherapy drugs

There are presented data illustrating sensitivity of gastrointestinal stromal tumors (GISTs) to certain chemotherapeutic agents (topoisomerase type II inhibitors, taxanes, vinca alkaloids) and pivaloyl-containing heterocyclic pyrroles (PCHPs). The chemotherapeutic drugs indicated above provided the cytotoxicity to IM-sensitive GIST cells. PCHPs were effective in both IM-sensitive, and resistant GISTs as well. Moreover PCHPs were also active against GISTs harboring the resistance to the chemotherapeutic agents indicated above. PCHPs-treated tumor cells underwent apoptosis due to the M-phase abnormalities and mitotic catastrophe.