At the Crossroads Between Neurodegeneration and Cancer: A Review of Overlapping Biology and Its Implications

Background: A growing body of epidemiologic evidence suggests that neurodegenerative diseases occur less frequently in cancer survivors, and vice versa. While unusual, this inverse comorbidity is biologically plausible and could be explained, in part, by the evolutionary tradeoffs made by neurons and cycling cells to optimize the performance of their very different functions. The two cell types utilize the same proteins and pathways in different, and sometimes opposite, ways. However, cancer and neurodegeneration also share many pathophysiological features. Objective: In this review, we compare three overlapping aspects of neurodegeneration and cancer. Method: First, we contrast the priorities and tradeoffs of dividing cells and neurons and how these manifest in disease. Second, we consider the hallmarks of biological aging that underlie both neurodegeneration and cancer. Finally, we utilize information from genetic databases to outline specific genes and pathways common to both diseases. Conclusion: We argue that a detailed understanding of the biologic and genetic relationships between cancer and neurodegeneration can guide future efforts in designing disease-modifying therapeutic interventions. Lastly, strategies that target aging may prevent or delay both conditions.