Anticancer Therapeutic Strategies Targeting p53 Aggregation

Abstract

p53 is a tumor suppressor protein that is mutated in more than 50% of cancer cases. When mutated, it frequently results in p53 oncogenic gain of function (GOF), resulting in a greater tendency to aggregate in the phase separation and phase transition pathway. GOFs related to p53 aggregation include chemoresistance, which makes therapy even more difficult. The therapies available for the treatment of cancer are still quite limited, so the study of new molecules and therapeutic targets focusing on p53 aggregates is a promising strategy against cancer. In this review, we classify anticancer molecules with antiaggregation properties into four categories: thiol alkylating agents, designed peptides, agents with chaperone-based mechanisms that inhibit p53 aggregation, and miscellaneous compounds with anti-protein aggregation properties that have been studied in neurodegenerative diseases. Furthermore, we highlight autophagy as a possible degradation pathway for aggregated p53. Here, considering cancer as a protein aggregation disease, we review strategies that have been used to disrupt p53 aggregates, leading to cancer regression.