TITLE:
New Immunological Approaches in Hepatocellular Carcinoma: Glypican-3 (GPC-3) Opportunities and Challenges
AUTHORS:
Bobby Varghese, Navid Darayan, Cristiana Rastellini, Luca Cicalese, Mauro Montalbano
KEYWORDS:
Glypican-3, Hepatocellular Carcinoma, Immunotherapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.11 No.11,
November
5,
2020
ABSTRACT: 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 used 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 are 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, due to
the existing gap in the literature surrounding GPC-3. The role GPC-3 plays in
the hepatocellular carcinoma phenotype can be targeted for a novel
immunotherapy strategy that can specify cell-mediated destruction of neoplastic
cell that spares normal liver tissue, and it can be exploited as a new serum
marker to trend for diagnosis and disease progression measurements. We believe
further investigation of its functions and structure, including alternative
cellular localizations, is necessary to evaluate GPC-3 as valuable target to
cure this cancer.