Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.

Hyaluronic acid (HA) is a major component of the extracellular matrix, providing essential mechanical scaffolding for cells and, at the same time, mediating essential biochemical signals required for tissue homeostasis. Many solid tumors are characterized by dysregulated HA metabolism, resulting in increased HA levels in cancer tissue. HA interacts with several cell surface receptors, such as CD44 and RHAMM, thus co-regulating important signaling pathways in cancer development and progression. In this review, we describe the enzymes controlling HA metabolism and its intracellular effectors emphasizing their impact in cancer chemotherapy resistance. We will also explore the current and future prospects of HA-based therapy, highlighting the opportunities and challenges in the field.