Anti-cancer target therapy based on drugs conjugated to hyaluronic acid

Abstract The number of cancer patients is constantly growing, and there is a need for novel more successful therapy. Understanding the difference between healthy and cancer cells is necessary for developing a new target therapy. A possible approach is the use of hyaluronic acid (HA, hyaluronan) that has an important role in the physiology and pathology of cancer cells. By bounding to CD44 and RHAMM receptors this acid participates in the signaling pathways that are involved in the pathogenesis and progression of cancer. Normal and malignant cells differ among themselves by the number of receptors expressed on the cell surface. Cancer cells have increased number of CD44 and RHAMM receptors in contrast to normal cells. HA is biocompatible, biodegradable, nontoxic, nonimmunogenic, can be easily chemically modified and used as a carrier for drugs and genes. Hyaluronic acid can be used in therapy creation in three different ways: 1.Targeting hyaluronan metabolism; 2.Targeting hyaladherins and 3. HA-based drug delivery systems. Hyaluronan is conjugated to paclitaxel, irinotecan, bisphosphonates, doxorubicin and cisplatin and conjugates designed for target therapy are obtained. Conjugates are intended for treatment when the drug alone does not show positive results, the cancer becomes resistant to the drug and the metastasizing cancer is accelerated. Conjugation of the drug with hyaluronan can be performed in different ways and each way has its positive sides, which improves the action of the drug in cancer cells. Conjugates are specifically linked only to CD44 receptors which are found in many cancer cells and allow normal cells to remain free without being affected. Through the corresponding receptors, the drugs conjugated with hyaluronan enter in the cells and exhibit its’ effect. Similar to drugs, nucleic acid can be conjugated and used for inactivation of cancer related genes. However, further researcher in these promising field is necessary. Key Words: hyaluronic acid, anti-cancer target therapy, CD44, RHAMM,HA-dru