While efforts are being made to identify the mechanisms of resistance and to develop novel drugs and therapeutic agents to overcome them the lack of physiologically relevant drug resistant cancer model systems remains a significant challenge drug resistance in cancer comes in two forms intrinsic resistance and acquired resistance. The lack of physiologically relevant drug resistant cancer model systems remains a significant challenge drug resistance in cancer comes in two forms intrinsic resistance and acquired resistance intrinsic resistance is present before a therapy. That is why combining treatments that have different mechanisms of action can kill more cancer cells and reduce the chance that drug resistance will emerge most of the research on drug resistance has focused on identifying genetic mechanisms such as mutations that alter a protein such that it impairs the binding of a drug. Two known models the cancer stem cell csc model and the environment mediated drug resistance emdr model which are not mutually exclusive could explain the origin of resistant cells in the csc model rare populations of cancer stem cells possess tumor initiating properties teicher 2006 nguyen et al 2012