fig1

Figure 1. Simplified scheme, summarizing various possibilities for drug resistance: (1) at oral administration gut uptake can be poor; (2) i.v. administration can be associated with extensive renal clearance or liver metabolic clearance by phase I and II enzymes; (3) from the tumor blood capillaries the drug can be taken up by either diffusion (single arrow), facilitated transport (tube) or active transport (cross); (4) in the cell the drug can be activated or inactivated; (5) these metabolites can be effluxed; (6) the drug can be sequestered (e.g., in the lysosome, where it can be protonated); (7) the drug can hit a protein kinase; (8) or DNA; (9) or other targets. The cell can respond to changes in any of these processes (either increase or decrease), activate alternative signaling pathways, modify the target, or repair the damage