Abstract:
Hepatocellular carcinoma (HCC) is the 5th most common type of cancer and, the 2nd cause of
cancer death in adult males after lung cancer. It contains 90% of the primary carcinoma of the liver.
There is no proper treatment available except surgeries and chemotherapies. This necessitates a
better understanding of the underlying mechanisms of the therapeutic targets and interventions for
the treatment of HCC. In the case of HCC, reactivation of telomerase expression increases the risk
by about 90% and it involves the uncontrolled cell proliferation of HSC cells. Previously various
HCC drugs have failed in clinical investigation mainly due to poor efficacy and target-disease
linkage. Therefore, the identification of potential drug targets and their impact on the biological
response could aid in the potential therapeutic intervention against HCC. Therefore, the
construction of a biological regulatory network of previously known biomarkers in HCC and their
responses were simulated. Subsequently, dynamic simulations were performed by JIMENA
software using two types of cells (normal and diseased) under different concentrations of nodes.
This study reveals that EGFR along with any combination might be used as a therapeutic target
for HCC. This research indicates the upregulation of hTERT, EGFR, and ADRB-2 receptors and
the downregulation of p53 and DYRK-3 in HCC.
Significantly, crucial cellular components such as ADRB-2, AKT, and ERK display increased
levels of activity when subjected to disturbance in diseased cells, indicating their possible
involvement in the development of HCC. The nodes associated with apoptosis are inhibited, while
cell proliferation reaches its peak activity after applying perturbation function, suggesting a
possible imbalance that promotes excessive cell growth and inhibits the normal process of cell
death in the disease condition. Key components in the advancement of cancer, including DYRK3,
EGFR, and hTERT, exhibit substantial modifications, suggesting their possible role as catalysts
in the behavior of abnormal cells. The triggering of SP1 introduces intricacy to the regulatory
framework of the network. In this study, different therapeutic targets have been identified and their
impact on the overall cellular response against hepatocellular carcinoma using systems biology
approaches.
