Opioids have been a mainstay for the management of cancer-related pain. However, recent clinical and basic research findings that will be explored with the audience have suggested that for many types of cancers, opioids promote tumor resistance and metastatic aggressiveness. Alternative future therapies may focus on other new areas of research advance that will be reviewed with the audience. This includes the generation of ectopic spontaneous discharges from primary sensory neuron somata and the sensitization of nociceptors by cancer cell derived exosomes. Findings from human tissue and experimental animal research will be reviewed.