Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma
| Autor: | Francesco Angelini, Michela Guardascione, Erika Cecchin, Luisa Foltran, Giuseppe Toffoli, Tania Di Raimo, Mario D'Andrea, Elena De Mattia |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Sorafenib medicine.medical_specialty Carcinoma Hepatocellular Cabozantinib Hepatocellular carcinoma Pyridines Antineoplastic Agents Review Pembrolizumab Palbociclib Immune checkpoint inhibitors 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Regorafenib Internal medicine Biomarkers Tumor medicine Humans Molecular Targeted Therapy Tivantinib Protein Kinase Inhibitors Polymorphism Genetic business.industry Patient Selection Phenylurea Compounds Liver Neoplasms Gastroenterology UDP glucuronosyltransferase 1A General Medicine Prognosis Progression-Free Survival digestive system diseases 3. Good health chemistry Pharmacogenetics Drug Resistance Neoplasm 030220 oncology & carcinogenesis Genetic markers Cytochromes 030211 gastroenterology & hepatology Nivolumab Lenvatinib business Metabolic Networks and Pathways medicine.drug |
| Zdroj: | World Journal of Gastroenterology |
| ISSN: | 1007-9327 |
| DOI: | 10.3748/wjg.v25.i29.3870 |
| Popis: | Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other small-molecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c-MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and critically discuss the pharmacogenetic literature evidences, with particular attention to sorafenib and regorafenib, which have been used longer than the others in HCC treatment. |
| Databáze: | OpenAIRE |
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