title: Targeting hyaluronic acid family for cancer chemoprevention and therapy.
abstract: Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer therapy. Furthermore, as these members are also overexpressed in a variety of carcinomas, targeting of the HA family is clinically relevant. A variety of targeted approaches have been developed to target various HA family members, including small-molecule inhibitors and antibody and vaccine therapies. These treatment approaches inhibit HA-mediated intracellular signaling that promotes tumor cell proliferation, motility, and invasion, as well as induction of endothelial cell functions. Being nontoxic, nonimmunogenic, and versatile for modifications, HA has been used in nanoparticle preparations for the targeted delivery of chemotherapy drugs and other anticancer compounds to tumor cells through interaction with cell-surface HA receptors. This review discusses basic and clinical translational aspects of targeting each HA family member and respective treatment approaches that have been described in the literature.
authors: Department of Urology, University of Miami-Miller School of Medicine, Miami, Florida, USA; Department of Cell Biology, University of Miami-Miller School of Medicine, Miami, Florida, USA; Miami Clinical Translational Institute, University of Miami-Miller School of Medicine, Miami, Florida, USA. Electronic address: vlokeshw@med.miami.edu.
authors: Vinata B
authors: VB
authors: Lokeshwar
authors: Department of Urology, University of Miami-Miller School of Medicine, Miami, Florida, USA.
authors: Summan
authors: S
authors: Mirza
authors: Sheila and David Funte Program in Cancer Biology, University of Miami-Miller School of Medicine, Miami, Florida, USA.
authors: Andre
authors: A
authors: Jordan
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry; D049109:Cell Proliferation; D004337:Drug Carriers; D016503:Drug Delivery Systems; D015195:Drug Design; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D009844:Oligosaccharides / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D004337:Drug Carriers; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D009844:Oligosaccharides; D034741:RNA, Small Interfering; C098946:hyaluronan-mediated motility receptor; D006820:Hyaluronic Acid
keywords: CD44; HA synthase; HYAL-1; Hyaluronic acid; RHAMM; Targeted cancer therapy