Chemotherapy neurotoxicity is codependent on cancer

Neurological disorders induced by chemotherapy, including pain and other debilitating sensory conditions correlate with alterations in diverse systemic, cellular, and molecular processes. Chemotherapeutic agents variously induce inflammatory responses, metabolic disorders and associated gene expression changes, all of which have the capacity to impact sensory function . Early evidence of independent effects by cancer alone on some of these same processes led us to hypothesize that neurological symptoms may emerge from cooperativity in the effects of chemotherapy and cancer. We tested this hypothesis in a rodent model of human colon cancer after a full course of human-scaled treatment with the commonly used chemotherapeutic agent oxaliplatin. Transcriptional profiling of dorsal root ganglia demonstrated that cancer and chemotherapy in combination produced changes that were unpredictable or undetectable from those observed with either alone. Unique combinatorial effects of chemotherapy and cancer were conserved as dysregulation of select ion-channel proteins and associated reduction in excitability of sensory neurons responsible for proprioception. Recognition of the non-additive interactions between chemotherapy and cancer may lead to the development of more effective strategies for the prevention and/or treatment of chronic neurological disorders commonly associated with cancer therapy. We used microarrays to detail the global programme of gene expression underlying neurologic dysfunction following chemotherapy treatment in animals bearing and not bearing cancer. In total, 13 (three groups with biologic triplicates per group and 4 biologic replicates from a final combinatorial group) global transcriptional expression data sets were generated in this study