Mechanistic Insights into Cell Death Mediated by the P53 Family

Development of effective anti-cancer therapies continues to be a challenge due to genetic instability that promotes intra-tumoral molecular heterogeneity and subsequent adaptation to therapy. In this review, we briefly discuss the history of the p53 family (p53/p63/p73) and how regulatory circuits affect its function in promoting apoptotic cell death. In addition, we provide perspective on how protein-protein interactions between members of the p53 family, as well as, with other regulatory proteins can dictate response to therapy. In the future, therapies that focus on targeting the p53 family to sustain pro-apoptotic pathways in combination with cancer-specific dysregulated signaling pathways is a promising approach. With further investigation at the basic science level, improvements in efficacy and quality of life for cancer patients with diverse molecular signatures may be realized.