Treating tyrosine kinase inhibitor resistant malignancies in patients with genetic polymorphisms or dysregulation or mutation of AHI1 using dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulucitol, or analogs or derivatives thereof How to

摘要

Methods and compositions suitable for treating malignant tumors in subjects with germline deletion polymorphisms that block the activity of thymidine kinase inhibitors in inducing apoptosis in tumor cells or subjects having AHI1 gene mutations or dysregulations Disclose. These methods include dianhydrogalactitol, dianhydrogalactitol derivatives or analogs, diacetyldianhydrogalactitol, diacetyldianhydrogalactitol derivatives or analogs, dibromodulucitol, and dibromodulcitol derivatives or analogs An alkylated hexitol derivative such as an analog is used. The composition can include such alkylated hexitol derivatives. The method can further include administration of a BH3 mimetic and the composition can further include a BH3 mimetic. In a subject having an AHI1 gene dysregulation, the method can further comprise administration of an agent that alters the expression or activity of the AHI1 gene or AHI1 protein, and the composition can further include such an agent.