Hepatocellular Carcinoma: Molecular Biology and Therapy
Section snippets
Cirrhosis and Scoring Systems
The presence of cirrhosis is an important factor to assess when evaluating any patient with HCC. Historically, medical oncologists have used the Child’s-Pugh Scoring System3, 4 which consists of five parameters: albumin, bilirubin, prothrombin time, and encephalopathy. Each of those parameters is given one to three points based on severity, and the addition of those points will lead to a score system, A, B or C, which helps define a patient’s outcome (Table 1). A limitation of the Child’s-Pugh
Chemotherapy
Many chemotherapeutic agents have been tested in HCC, mainly in phase II studies evaluating response. Response rates ranging from 10% to 20%9, 10, 11 have been reported, but no clear impact on survival has been identified.
The most studied chemotherapeutic agent is doxorubicin (adriamycin), with a response rate of 11%.12 The regimen that has shown the highest response in HCC is the combination of cisplatin, interferon, doxorubicin, and 5-fluorouracil (PIAF), which showed a 26% response rate and
Molecular Concepts
In recent years, investigators have achieved a better understanding of the molecular events leading to oncogenesis of HCC. In parallel, multiple novel therapeutic agents are being assessed in HCC.
With regard to etiology, as an example, chronic hepatitis can lead to phenotypically altered hepatocytes and ultimately cirrhosis. Occasionally, chronic hepatitis B leads to HCC without the interval development of cirrhosis. Phenotypically altered hepatocytes have high epidermal growth factor receptor
Novel Therapeutics
Many novel therapeutic agents for HCC have been evaluated in phase I and II studies. Sorafenib (Nexavar; Bayer, West Haven, CT and Onyx, Bellevue, WA), erlotinib (Tarceva; OSI Oncology, Melville, NY), bevacizumab (Avastin; Genentech, San Francisco, CA), and flavopiridol will be discussed herein. Sorafenib is a Raf kinase inhibitor with anti-vascular endothelial growth factor and anti–platelet-derived growth factor activity.19 Vascular endothelial growth factor and platelet-derived growth factor
Conclusion
Management of advanced and metastatic HCC continues to be challenging because of high expression of drug resistance genes, underlying cirrhosis, and poor liver function in many patients. Functional scoring of the cirrhosis and the HCC is a critical part of evaluating a patient with HCC. The CLIP scoring system should be used for patients with a hepatitis C etiology, and the CUPI scoring system is optimal for patients with hepatitis B-related HCC.
Thus far, no cytotoxic agent has been shown to
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