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Published on: September 30, 2021
Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges
Monica A Kamal1, Yasmine M Mandour2, Mostafa K Abd El-Aziz1
1The Molecular Pharmacology Research Group, Department of Pharmacology, Toxicology and Clinical Pharmacy, Faculty of Pharmacy and Biotechnology, German University in Cairo-GUC, Cairo 11835, Egypt.
Abstract:
According to data provided by World Health Organization, hepatocellular carcinoma (HCC) is the sixth most common cause of deaths due to cancer worldwide. Tremendous progress has been achieved over the last 10 years developing novel agents for HCC treatment, including small-molecule kinase inhibitors. Several small molecule inhibitors currently form the core of HCC treatment due to their versatility since they would be more easily absorbed and have higher oral bioavailability, thus easier to formulate and administer to patients. In addition, they can be altered structurally to have greater volumes of distribution, allowing them to block extravascular molecular targets and to accumulate in a high concentration in the tumor microenvironment. Moreover, they can be designed to have shortened half-lives to control for immune-related adverse events. Most importantly, they would spare patients, healthcare institutions, and society as a whole from the burden of high drug costs. The present review provides an overview of the pharmaceutical compounds that are licensed for HCC treatment and other emerging compounds that are still investigated in preclinical and clinical trials. These molecules are targeting different molecular targets and pathways that are proven to be involved in the pathogenesis of the disease.
Insights
Small-molecule kinase inhibitors are revolutionizing hepatocellular carcinoma (HCC) treatment. These versatile oral drugs offer improved bioavailability, targeted delivery, and reduced costs, improving patient outcomes for this common cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) ranks as the sixth leading cause of cancer-related mortality globally.
- Recent advancements in HCC therapy focus on novel agents, particularly small-molecule kinase inhibitors.
Purpose of the Study:
- To review currently licensed and emerging pharmaceutical compounds for hepatocellular carcinoma (HCC) treatment.
- To highlight the molecular targets and pathways implicated in HCC pathogenesis addressed by these agents.
Main Methods:
- Literature review of licensed and investigational drugs for HCC.
- Analysis of the pharmacological properties and mechanisms of action of small-molecule inhibitors.
- Examination of clinical trial data and preclinical investigations.
Main Results:
- Small-molecule inhibitors offer advantages such as enhanced oral bioavailability, targeted tumor accumulation, and controllable half-lives.
- These agents can be structurally modified for improved distribution and to mitigate immune-related adverse events.
- The development of these drugs aims to reduce the economic burden on patients and healthcare systems.
Conclusions:
- Small-molecule kinase inhibitors represent a significant advancement in HCC treatment, offering versatile and potentially cost-effective therapeutic options.
- Ongoing research into novel compounds targeting specific molecular pathways continues to expand the therapeutic landscape for HCC.
- These targeted therapies hold promise for improving patient outcomes and managing immune-related adverse events in HCC management.
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