The article discusses the complex mechanisms that regulate cell death in response to p53, a tumor suppressor protein. Cancer cells are highly sensitive to apoptotic signals but survive due to lesions that prevent or impede cell death, such as loss of p53 function. The authors highlight the importance of understanding how tumor cells become resistant to apoptosis and how this knowledge can be used to develop therapeutic strategies. They explain that p53 can induce various responses, including cell-cycle arrest, senescence, differentiation, and apoptosis, depending on intrinsic and extrinsic factors. The article also covers the mechanisms by which p53 loss occurs in cancers, including mutations in the TP53 gene and disruptions in pathways that mediate the p53 response. Additionally, it explores the role of p53 in regulating gene expression and its interaction with other proteins, such as MDM2, p63, and p73. The authors discuss the regulation of p53 activity, including phosphorylation and subcellular localization, and the role of survival signals in modulating the p53-induced apoptotic response. Finally, they emphasize the potential of targeting p53's cofactors and regulators for cancer therapy, suggesting that reactivating p53 function in cancer cells could be a promising therapeutic approach.The article discusses the complex mechanisms that regulate cell death in response to p53, a tumor suppressor protein. Cancer cells are highly sensitive to apoptotic signals but survive due to lesions that prevent or impede cell death, such as loss of p53 function. The authors highlight the importance of understanding how tumor cells become resistant to apoptosis and how this knowledge can be used to develop therapeutic strategies. They explain that p53 can induce various responses, including cell-cycle arrest, senescence, differentiation, and apoptosis, depending on intrinsic and extrinsic factors. The article also covers the mechanisms by which p53 loss occurs in cancers, including mutations in the TP53 gene and disruptions in pathways that mediate the p53 response. Additionally, it explores the role of p53 in regulating gene expression and its interaction with other proteins, such as MDM2, p63, and p73. The authors discuss the regulation of p53 activity, including phosphorylation and subcellular localization, and the role of survival signals in modulating the p53-induced apoptotic response. Finally, they emphasize the potential of targeting p53's cofactors and regulators for cancer therapy, suggesting that reactivating p53 function in cancer cells could be a promising therapeutic approach.