Chapter 12 - Pharmacodynamic biomarker for Hepatocellular carcinoma C: Model-based evaluation for pharmacokinetic–pharmacodynamic responses of drug

Abstract

Hepatocellular carcinoma (HCC) is the second most important cause of liver cancer mortality across the globe. More than 7,00,000 new cases occur every year of HCC. Liver cirrhosis, mostly occurs due to chronic hepatitis B and C infection, is a major cause of hepatocarcinogenesis. The occurrence of HCC is usually associated with three different stages—nonalcoholic fatty acid, nonalcoholic steatohepatitis, and cirrhosis. Most of the patients are observed with advanced stages of HCC at the time of screening. Despite its high prevalence, its etiology is unclear, and also the disease-adjusting medications are inaccessible for patients with an advanced stage of HCC. Hence, there is an immediate urgency of improving the early detection and also the prognostication of patients suffering from HCC. Pharmacodynamic biomarkers are indicators for the assessment of the molecular linkage between drug regimen and target response. Recently, some novel pharmacodynamic biomarkers such as hepatocyte growth factor and fibroblast growth factor have been developed in response to sorafenib (an FDA-approved drug for HCC treatment). But the survival rates posttreatment with sorafenib are limited (2–5 months), and the other drugs such as lenvatinib, cabozantinib, and ramucirumab are still under clinical trials. Therefore it is imperative to focus on new potential pharmacodynamic biomarkers to study the pharmacokinetic–pharmacodynamic responses of the latest and existing drugs to have an effective treatment for advanced-stage HCC. In addition to this, the advancement of new therapies specific to target pathways involved in the progression of HCC should be the main aim for future research perspectives. In this chapter, we have discussed the utility and effectiveness of pharmacodynamic biomarkers using various animal models, and we have also analyzed the association of drug-target interaction and biological response against HCC.