The cross talk between protein misfolding and tumor microenvironment dynamics

Protein misfolding is a process in which an amino acid chain fails to attain its correct three-dimensional conformation, leading to structural abnormalities and functional impairment. This phenomenon plays a crucial role in various pathological conditions, including cancer, where it contributes to disease progression and cellular dysfunction. Cancer cells often secrete misfolded proteins, which actively interact with the tumor microenvironment (TME)-a complex network of stromal cells, immune cells, fibroblasts, and tumor cells-to influence key oncogenic processes. The consequences of protein misfolding extend beyond mere structural anomalies; they can drive tumorigenesis by enhancing cell proliferation, promoting metastasis, suppressing immune responses, and inducing chemoresistance. Given these critical implications, understanding the interplay between misfolded proteins and the TME offers valuable insights for therapeutic advancements. This chapter explores the molecular basis of protein misfolding, its role in modulating the TME, its impact on cancer progression, and emerging therapeutic strategies. Additionally, selected case studies are presented to highlight real-world applications of these concepts in cancer treatment and research.