Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review

Abstract

Hyaluronic acid (HA) is a linear polysaccharide and crucial component of the extracellular matrix (ECM), maintaining tissue hydration and tension. Moreover, HA contributes to embryonic development, healing, inflammation, and cancerogenesis. This review summarizes new research on the metabolism and interactions of HA with its binding proteins, known as hyaladherins (CD44, RHAMM), revealing the molecular basis for its distinct biological function in the development of cancer. The presence of HA on the surface of tumor cells is a sign of an adverse prognosis. The involvement of HA in malignancy has been extensively investigated using cancer-free naked mole rats as a model. The HA metabolic components are examined for their potential impact on promoting or inhibiting tumor formation, proliferation, invasion, and metastatic spread. High molecular weight HA is associated with homeostasis and protective action due to its ability to preserve tissue integrity. In contrast, low molecular weight HA indicates a pathological condition in the tissue and plays a role in pro-oncogenic activity. A systematic approach might uncover processes related to cancer growth, establish novel prognostic indicators, and identify potential targets for treatment action.

The Matrix Reloaded—The Role of the Extracellular Matrix in Cancer

“…HA turnover occurs in various molecular weights of HA distinguished by their polymer length, e.g., high-molecular-weight HA (Mw > 1.8 × 10 6 Dalton) and low-molecular-weight HA, Mw 4–10 × 10 5 Dalton), The molecular weight of HA determines its activities. High-molecular weight HA inhibits mitogenic processes and possesses anti-inflammatory effects, whereas low-molecular weight-HA shows protumorigenic effects by enhancing proliferation and inflammation [ 58 ].…”

“…A few clinical trials are currently evaluating the therapeutic effects of combining hyaluronidase and chemotherapeutics ( Table 2 ). PEGPH20 showed clinical benefits with chemotherapy in PDAC in a phase 2 trial but did not show any clinical benefit in phase 3 trials [ 58 ].…”

Targeted Delivery of Gemcitabine for Precision Therapy of Cholangiocarcinoma Using Hyaluronic Acid-Modified Metal–Organic Framework Nanoparticles

“…9−11 In the case of CCA patients, researchers are gradually focusing on more targeted and safer drugs, as well as comprehensive treatment methods such as biological and gene therapies. 12 Metal−organic frameworks (MOFs) have been widely used in the field of drug delivery due to their ease of functionalization, tunable pore sizes, and flexible compositions. This is because MOFs can control particle size, surface chemistry, and internal porosity, enabling the design of complex materials based on MOFs.…”

Mixtures of Doxorubicin-Loaded Micelles and Berberine and Mifepristone Co-Loaded Liposomes Inhibit Breast Cancer Metastasis Based on Regulation of Tumor Microenvironments

“…for co-delivering two and three drugs with different anti-tumor mechanisms have exhibited great potential in the treatment of breast cancer. − To improve active-targeting delivery, the vehicles were modified by different moieties, such as antibodies, polysaccharides, and various small-molecular ligands. Recent studies revealed that hyaluronic acid (HA) or chondroitin sulfate (CS) was used to modify nanosized carriers for tumor-targeting drug delivery by HA/CS-CD44 receptor-mediated endocytosis. − Considering that CD44 receptors were highly expressed on breast cells, HA-modified vehicles could enhance drug internalization in the treatment of breast cancer …”