Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies
Open accessAbstract
Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide. HCC is a complex process that is associated with several etiological factors, which in turn result in aberrant activation of different cellular and molecular pathways and the disruption of balance between activation and inactivation of protooncogenes and tumor suppressor genes, respectively. Since HCC most often occurs in the setting of a diseased or cirrhotic liver and most of the patients are diagnosed at the late stage of disease, prognosis is generally poor. At present, limited treatment options with marginal clinical benefits are available. Systemic therapy, particularly in the form of conventional cytotoxic drugs, are generally ineffective. In recent years, molecular-targeted therapies have been clinically used to treat various cancers, including liver cancer. This approach inhibits the growth of tumor cells by interfering with molecules that are involved in carcinogenesis, which makes it more selective and specific than cytotoxic chemotherapy. Many clinical trials have been carried out while using molecular targeted drugs in advanced HCC with many more in progress. The clinical trials in HCC to date have evaluated a single-targeted therapy alone, or two or more targeted therapies in parallel. The aim of this review is to provide insight of various molecular mechanisms, leading to HCC development and progression, and also the range of experimental therapeutics for patients with advanced HCC. The review will summarize different clinical trials data the successes and failures of these treatments, as well as the most effective and approved drugs designed against HCC.
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Inhibition of HIF-α hydroxylation can be achieved using PHD inhibitors, including Roxadustat, which is approved in China and Europe for the treatment of renal anemia in CKD, and daprodustat, vadadustat, enarodustat and molidustat, which have been approved in Japan.
“As such, inhibition of HIF-α hydroxylation can be achieved using PHD inhibitors, such as Roxadustat, which is approved in China and Europe for the treatment of renal anemia in CKD, and other PHD inhibitors, daprodustat, vadadustat, enarodustat and molidustat, which have been approved in Japan.637–642”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [641]
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
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- Authors
- Alqahtani, A., Khan, Z., Alloghbi, A., S. Said Ahmed, T., Ashraf, M., & M. Hammouda, D.
- Affiliations
- University of Toledo (US)
- The University of Texas Health Science Center at Houston (US)
- Department of Internal Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA
- Division of Hematology and Medical Oncology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA
- Corresponding author
- Alqahtani, Ali
- Venue
- Medicina
- Publisher
- MDPI AG
- Published
- 2019-08-23
- Volume
- 55
- Issue
- 9
- Pages
- 526
- ISSN
- 1010-660X (ISSN-L)
- 1648-9144
- PMC
- PMC6780754
- OpenAlex
- W2969744830
- Cited by
- 265
- References
- 68
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 51 · 2023: 46 · 2022: 70 · 2021: 28 · 2020: 21 · 2019: 1
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Medicina (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatocellular carcinoma, carcinogenesis mechanisms, targeted therapy, tumor suppressor, proto-oncogenes, advanced liver cancer, clinical trials, liver cirrhosis, tumor progression
- MeSH terms
- Antineoplastic Agents, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Risk Factors, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Incidence, Transforming Growth Factor alpha, NF-kappa B
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