^{Genomics and Molecular Biology}

Current clinical research in oncology has transitioned from a focus on generally cytotoxic chemotherapies to targeted, small molecule therapeutics. However, the broad array of gene repair and immune defense mechanisms in the body’s arsenal against cancer indicate that cancer is not simply the result of a single renegade cell randomly mutating out of control. Th e fact that genomewide epigenetic changes precede cancer, suggests that tumor etiology and progression involve multiple dynamical systems. One of the biological systems that have received the least attention in cancer research is that of the endogenous bioelectric signals stemming from ion channels in cell and mitochondrial membranes. Th ese voltage potentials have been shown to play an important

role in regulating cell diff erentiation, proliferation, migration, orientation, apoptosis and gene expression. In fact, one of the fi rst steps in the epithelial-mesenchymal transition in tumor formation is cellular depolarization. Not only does hyperpolarization of oncogenes prevent tumor development, it has been demonstrated that bioelectric signals interact with biochemical signaling, and that depolarized Vmem is an epigenetic initiator of metastatic behavior even in the absence of a centralized tumor. Th e theme of this talk is that for cancer to occur, multiple systems must be dysfunctional and that biophysical signaling fi lls an important knowledge gap in current thinking in tumor biology.