Background: Hyaluronan (HA), a glycosaminoglycan, is a key extracellular matrix (ECM)
component, and has been established to contribute to fibrotic, angiogenic, inflammatory as well as
processes supporting cancer development. The changes in HA deposition in different tumors have been
widely studied. Indeed, a multitude of reports demonstrate that HA expression is increased in different
neoplasmatic tissues including lung, colon, prostate and breast cancer. The aims of this paper are to
critically and in depth discuss aspects of HA metabolism in cancer and recent developments of its
utilization in cancer therapy.
Methods: Up to date research and online content are reviewed.
Results: The cellular roles of HA are perpetrated through molecular interactions with HA-binding proteins, called hyaladherins,
including CD44 receptor as well as receptor for hyaluronan-mediated motility (RHAMM). HA binding can be followed
by receptor-mediated endocytosis. Importantly, hyaladherins show an altered expression in tumor tissues. Indeed,
post-translational alterations in CD44 structure have been suggested to regulate the equilibrium between the “inactive”
low affinity state and the “active” high affinity state of the HA binding capacity. In this concept HA fragments can be utilized
as specific targeting ligands for efficient and safe drug delivery in cancer.
Conclusion: HA-drug bioconjugates and nanoparticles have emerged as a promising platform for drug delivery during
cancer treatment as demonstrated in various pre-clinical studies. Recent developments from clinical trials indicate that the
utilization of specific HA-drug bioconjugates might be approved for the medical practice in the nearest future.