Targeting Hyaluronic Acid and Peritoneal Dissemination in Colorectal Cancer |
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| Affiliation: | 1. Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, School of Medicine, Cardiff University;2. Cardiff and Vale University Health Board;1. Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia;2. Sir PeterMacCallum Department of Oncology, University of Melbourne, Parkville, Australia;3. Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia;4. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia;1. New York-Presbyterian/Weill Cornell Medicine, New York, NY;2. Division of Colorectal Surgery, Department of Surgery, University of California,Irvine Medical Center, CA;3. Department of Medicine, Division of Oncology, University of California, Irvine Medical Center, CA;1. Institut des Maladies de l''Appareil Digestif, Digestive Oncology Unit, University Hospital, Nantes, France;2. Department of Pathology, University Hospital, Nantes, France;3. Department of Pharmacy, University Hospital, Nantes, France;1. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China;2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China |
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| Abstract: | Peritoneal metastasis (PM) from colorectal cancer (CRC) carries a significant mortality rate for patients and treatment is challenging. The development of PM is a multistep process involving detachment, adhesion, invasion and colonization of the peritoneal cavity. Cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy) for PM from CRC has some benefit but overall survival is poor and recurrence rates are high. Treatments to prevent the development of peritoneal metastasis could have the potential to improve CRC survival and disease-free outcomes.The ability of cancer cells to invade the peritoneum and become established as metastatic tumors is influenced by a multifactorial process. Hyaluronic acid (HA) has been shown to coat the mesothelial cells of the peritoneum and has been demonstrated to be utilized in various malignancies as part of the metastatic process in peritoneal dissemination. CD44, RHAMM (CD168) and ICAM-1 have all been shown to be binding partners for HA. Targeting HA-mediated binding may prevent adhesion to distant sites within the peritoneum through suppression of interaction of these molecules. Here we review the current literature and discuss key molecules involved with PM dissemination, with the potential to target these mechanisms in the delivery of future treatments. |
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