Hyaluronic acid as a tumor progression agent and a potential chemotherapeutic biomolecule against cancer: A review on its dual role

Hyaluronic acid is a major constituent of the extracellular matrix of vertebrate tissue that provides mechanical support to cells and acts as a mediator in regulation of necessary biochemical process essential for maintenance of tissue homeostasis. The variation in quantity of hyaluronic acid content in tissues is often associated with different pathological conditions. It is associated with tumor aggression and progression as it plays crucial role in regulating different aspects of tumorigenesis and several defined hallmarks of cancer. It assists in tumor progression by undergoing extracellular remodeling to establish tumor microenvironment which restricts the delivery of cytotoxic drugs to neoplastic cells due to increase in interstitial pressure. Hyaluronic acid catabolic and anabolic genes and low-molecular weight hyaluronic acid play significant role in the establishing tumor microenvironment by assisting in cell proliferation, metastasis and invasion. On the other hand, it is also used as an effective drug-delivery platform in cancer therapies as its biocompatibility and biodegradability lower the toxicity of chemotherapeutic drugs and increase drug retention. High-molecular weight hyaluronic acid-bioconjugates specifically bind with hyaladherins, facilitating targeted drug delivery and also exert anti-inflammatory properties. This review also highlights the market and patent trends in the development of effective chemotherapeutic hyaluronic acid formulations and the current scenario regarding clinical trials.