New Immunological Approaches in Hepatocellular Carcinoma: Glypican-3 (GPC-3) Opportunities and Challenges

• 作者: Bobby Varghese Cristiana Rastellini Luca Cicalese Mauro Montalbano Navid Darayan
• 来源期刊: 癌症治疗(英文)
• 学科: 医学
• 关键词: GLYPICAN-3 Hepatocellular Carcinoma IMMUNOTHERAPY
• 年，卷（期）: 2020,（11）
• 页码范围: 647-659
• 页数: 13页
• 分类号: R73

摘要

Immunotherapy is one of the strategies to boost natural defenses to fight cancer. Immuno-oncology is an artificial stimulation of the human immune system to recognize and kill selectively neoplastic cells at different stage of transformation. Cancer cells have tumor antigens and the antibody of the immune system, binding them, can detect molecules on their extracellular side of cell membrane. Among these proteins, it is rising in interest and use<span style="font-family:Verdana;">d</span><span style="font-family:Verdana;"> for early detection of hepatocellular carcinoma (HCC) Glypican-3 (GPC-3) protein. It is a heparan sulfate proteoglycan (HSPG), anchored to the cell membrane of transformed hepatocytes. We investigated its function as key regulator of hepatocytes neoplastic transformation. Noteworthy, GPC-3 protein has been implicated in different pathways from cell growth to cell motility and migration. More recently, GPC-3 has been evaluated as a useful marker for HCC due to its increased expression in the liver during tumorigenesis and its absence in normal liver. Immunotherapy that targets GPC-3 domains and its connected proteins </span><span style="font-family:Verdana;">are</span><span style="font-family:Verdana;"> currently under investigation. These new biomarkers may hold potential for the detection and treatment of HCC and other diseases in which GPC-3 may be overexpressed and/or play a crucial role. This review will summarize the current knowledge regarding the active immunotherapy developed to treat HCC and it will evaluate aspects of GPC-3 (structure and biology) as advantages and potential pitfalls for considering it as a valuable immunotherapeutic target. We also elaborated the current literature with the aim to better understand its biological interactions at a molecular and cellular level to identify alternative or combined targets</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> due to the existing gap in the literature surrounding GPC-3. The role GPC-3 plays