Fibrosis and cancer: A strained relationship

Fibrotic tumors are the result of excessive deposition, remodeling, and cross-linking of the extracellular matrix (ECM). This altered ECM exerts mechanical forces that reciprocally alter tumor cell behavior and fate, and correlate with disease progression and patient survival. In this review, we discuss the mechanoreciprocity between tumor cells, cancer associated fibroblasts (CAF), immune cells and the ECM. We present recent evidence that tumor cells and CAFs engineer the fibrotic tumor stroma, that different CAF subtypes uniquely affect tumor evolution, and how mechanoreciprocity between tumor cells, CAFs, immune cells, and the ECM, drives tumor aggression and evolution. Finally, we highlight key studies that demonstrate the dynamic mechanoreciprocity in breast and pancreatic cancer, and discuss potential therapies to target fibrosis in cancer treatment.