The role of TRPM2 in the pathways of various inhibitors and activators. (a) A schematic illustration of the TRPM2 channel which includes 4 N-terminal MHR domains, six transmembrane helices labelled S1–S6, a TRP domain, a coiled-coil domain and NUDT9-H domain. (b) BTX increases mitochondrial ROS leading to increased caspase 9 and 3. (c) The pathway of TNF-α, increasing ROS, activating the caspase 8 cascade, increasing ROS in the mitochondria, finally leading to increased PARP. PARP converts NAD+ to ADPR, activating TRPM2 at the NUDT9-H domain, in turn allowing for Ca2+ influx. (d) Resveratrol as an adjuvant therapy with paclitaxel heightens the apoptotic affects of paclitaxel via activation of the caspase 9 and 3 cascades while increasing PARP for downstream effects as previously described . (d) Curcumin inhibits TRPM2 via inhibition of the PARP1. (f) Selenium increases the apoptotic ability of docetaxel via activation of TRPM2 channels, increasing PARP and ROS in the mitochondria, for increased ADPR production. (g) H2O2 and ROS increase ROS and increase PARP, augmenting ADPR expression and TRPM2 activation.