Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death

Currently, research in anti-cancer therapy remains a priority. This is driven by two main challenges: the difficulty of modeling and developing targeted or precision drugs and the multiple, often unpredictable, body responses to treatment. The primary objective of modern anti-cancer drugs is the induction of cancer cell death. One of the key regulators of cell death is the tumor suppressor protein p53. This protein is a well-known transcription factor encoded by <i>TP53</i>. Despite the fact that p53 is generally considered a pro-apoptotic inducer, it also regulates cell death pathways such as necrosis and autophagy. Given the diversity of p53-mediated cell death pathways, establishing a specific activated mechanism is a necessary step in developing effective anti-cancer drugs, since certain types of cell death can cause adverse outcomes in patients, including infection, sepsis, tumor progression and metastasis. The review summarizes knowledge about p53-dependent cell death mechanisms and the p53 transcriptional targets that are involved. It also describes shared molecular pathways among apoptosis, necrosis, and autophagy, as well as the methods and markers used to distinguish one type of cell death from another.