TY - JOUR
T1 - Systemic therapy for advanced hepatocellular carcinoma
T2 - targeted therapies
AU - Tella, Sri Harsha
AU - Kommalapati, Anuhya
AU - Mahipal, Amit
N1 - Publisher Copyright:
© Chinese Clinical Oncology. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Therapeutic options for advanced, unresectable hepatocellular carcinoma (HCC) have changed dramatically over the last 3 years. While surgical resection, orthotropic liver transplantation, and localized therapeutic options such as ablation, radiation therapy, and embolization remain therapeutics of choice in localized disease, systemic therapy is the only option in advanced, metastatic HCC. Since the United States Food and Drug Administration (US FDA) approval of sorafenib in 2008, targeted therapies such as sunitinib, tivantinib, brivanib, erlotinib, and linifanib; monoclonal antibody- bevacizumab showed no meaningful improvement in treatment of HCC. However, with improved understanding on the molecular pathophysiology and tumor heterogeneity of HCC, we have made progress in expanding the therapeutic options in advanced HCC. Targeted therapy with lenvatinib, cabozantinib, and regorafenib; monoclonal antibody ramucirumab; immunotherapies nivolumab and pembrolizumab have demonstrated promising results in the clinical trials. The current work outlines the molecular mechanisms and tumorigenesis of HCC, a detailed discussion of the trial results of the approved therapies in HCC, future perspectives and potential options to overcome the challenges of systemic therapy in HCC.
AB - Therapeutic options for advanced, unresectable hepatocellular carcinoma (HCC) have changed dramatically over the last 3 years. While surgical resection, orthotropic liver transplantation, and localized therapeutic options such as ablation, radiation therapy, and embolization remain therapeutics of choice in localized disease, systemic therapy is the only option in advanced, metastatic HCC. Since the United States Food and Drug Administration (US FDA) approval of sorafenib in 2008, targeted therapies such as sunitinib, tivantinib, brivanib, erlotinib, and linifanib; monoclonal antibody- bevacizumab showed no meaningful improvement in treatment of HCC. However, with improved understanding on the molecular pathophysiology and tumor heterogeneity of HCC, we have made progress in expanding the therapeutic options in advanced HCC. Targeted therapy with lenvatinib, cabozantinib, and regorafenib; monoclonal antibody ramucirumab; immunotherapies nivolumab and pembrolizumab have demonstrated promising results in the clinical trials. The current work outlines the molecular mechanisms and tumorigenesis of HCC, a detailed discussion of the trial results of the approved therapies in HCC, future perspectives and potential options to overcome the challenges of systemic therapy in HCC.
KW - Lenvatinib
KW - Liver cancer
KW - Sorafenib
KW - Targeted therapy
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U2 - 10.21037/CCO-20-117
DO - 10.21037/CCO-20-117
M3 - Review article
C2 - 32434345
AN - SCOPUS:85100629803
SN - 2304-3865
VL - 10
JO - Chinese clinical oncology
JF - Chinese clinical oncology
IS - 1
M1 - 10
ER -