Advancements in Hepatocellular Carcinoma: Potential Preclinical Drugs and their Future

Abstract

Hepatocellular carcinoma (HCC) is one of the foremost causes of tumor-affiliated demises globally. The HCC treatment has undergone numerous developments in terms of both drug and non-drug treatments. The United States Food and Drug Administration (FDA) has authorized the usage of a variety of drugs for the treatment of HCC in recent years, involving multi-kinase inhibitors (lenvatinib, regorafenib, ramucirumab, and cabozantinib), immune checkpoint inhibitors (ICIs) (pembrolizumab and nivolumab), and combination therapies like atezolizumab along with bevacizumab. There are currently over a thousand ongoing clinical and pre-clinical studies for novel HCC drugs, which portrays a competent setting in the field. This review discusses the FDA-approved HCC drugs, their molecular targets, safety profiles, and potential disadvantages; ii. The in-trial agents/drugs, their molecular targets, and possible benefits compared to alternatives, and iii—the current and future status of potential preclinical drugs with novel therapeutic targets for HCC. Consequently, existing drug treatments and novel strategies with their balanced consumption could ensure a promising future for a universal remedy of HCC in the near future.

Atezolizumab Plus Bevacizumab Versus Lenvatinib for Hepatocellular Carcinoma: A Systematic Review and Meta‐Analysis

“…In 2020, a new combination approach of ATE plus BEV was shown to be more beneficial than other first‐line drugs due to their favorable safety profiles in advanced HCC patients 26 . ATE/BEV is associated with better PFS, OS, response rate, and preservation of quality of life than sorafenib (IMbrave150) 27 .…”

“…25 In 2020, a new combination approach of ATE plus BEV was shown to be more beneficial than other first-line drugs due to their favorable safety profiles in advanced HCC patients. 26 ATE/BEV is associated with better PFS, OS, response rate, and preservation of quality of life than sorafenib (IMbrave150). 27 Targeting the tumor immune microenvironment by dual blockade of vascular endothelial growth factor and anti-programmed cell death-ligand 1using BEV and ATE, respectively, has been reported to provide a longer PFS for unresectable HCC than anti-programmed cell death-ligand 1 blockade alone.…”

Identification of a prognostic evaluator from glutamine metabolic heterogeneity studies within and between tissues in hepatocellular carcinoma

“…Most HCC cases occur in Asia, and the main known risk factors relevant to HCC are viruses (chronic hepatitis B and C), metabolism disorders (diabetes and non-alcoholic fatty liver disease, or NAFLD), toxicity (alcohol and aflatoxin), and immune system-related diseases (Chakraborty and Sarkar, 2022). The United States Food and Drug Administration approved liver cancer treatment options involving multi-kinase inhibitors (lenvatinib, regorafenib, ramucirumab, and cabozantinib), immune checkpoint blockades (ICBs) (pembrolizumab and nivolumab), and combination therapies, such as atezolizumab along with bevacizumab (Butt and Baytas, 2023). Although substantial breakthroughs have been made in systemic treatment, the mortality rate of HCC has remained high owing to drug resistance and frequent relapse (Chidambaranathan-Reghupaty et al, 2021;Chen et al, 2023).…”