More than Just Protein Folding: The Epichaperome, Mastermind of the Cancer Cell

The epichaperome, a dynamic and integrated network of chaperone proteins, extends its roles beyond basic protein folding to protein stabilization and intracellular signal transduction to orchestrating a multitude of cellular processes critical for tumor survival. In this review, we explore the multifaceted roles of the epichaperome, delving into its diverse cellular locations, factors that modulate its formation and function, its liquid-liquid phase separation, and the key signaling and crosstalk pathways it regulates, including cellular metabolism and intracellular signal transduction. We further highlight techniques for isolating and identifying epichaperome networks, pitfalls, and opportunities. Further, we review the profound implications of the epichaperome for cancer treatment and therapy design, underscoring the need for strategic engineering that hinges on a comprehensive insight into the comprehensive structure and workings of the epichaperome across the heterogeneous cell subpopulations in the tumor milieu. By presenting a holistic view of the epichaperome's functions and mechanisms, we aim to underscore its potential as a key target for novel anti-cancer strategies, revealing that the epichaperome is not merely a piece of protein folding machinery but a mastermind that facilitates the malignant phenotype.