Abstract
The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresectable or metastatic HCC. Currently, ongoing clinical trials with immune checkpoint blockade (ICB) have focused on assessing the benefit of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) as monotherapies or combination therapies in patients with HCC. In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.
Highlights
Hepatocellular carcinoma (HCC) is a primary malignant disease of the liver
Oncolytic immunotherapy has arisen as a promising approach for inhibiting tumor progression and metastasis [8]. The justification of this approach relates to enhancing cellular or humoral immunity via activating tumorspecific immune responses and disrupting immune tolerance. Developments in this field have led to many Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors (ICI) as primary treatment options for several different solid and hematologic malignancies [9]
Cytotoxic Tlymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), B and T lymphocyte attenuator (BTLA), V-domain immunoglobulin suppressor of T cell activation (VISTA), T-cell immunoglobulin and mucin domain 3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and tumor necrosis factor receptor superfamily member 4 (OX40) are the main ICIs under investigation [12]. It is a promising treatment modality for a variety of cancers, tumors often exhibit primary, adaptive, or acquired resistance to immunotherapy which might be intrinsic to the tumor cells or that may be influenced by their microenvironment [13]
Summary
Hepatocellular carcinoma (HCC) is a primary malignant disease of the liver. Primary liver cancer is the seventh most common malignancy and the second most frequent cancer-related death worldwide [1]. The justification of this approach relates to enhancing cellular or humoral immunity via activating tumorspecific immune responses and disrupting immune tolerance Developments in this field have led to many FDA approvals of immune checkpoint inhibitors (ICI) as primary treatment options for several different solid and hematologic malignancies [9]. (PD-L1), B and T lymphocyte attenuator (BTLA), V-domain immunoglobulin suppressor of T cell activation (VISTA), T-cell immunoglobulin and mucin domain 3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and tumor necrosis factor receptor superfamily member 4 (OX40) are the main ICIs under investigation [12] It is a promising treatment modality for a variety of cancers, tumors often exhibit primary, adaptive, or acquired resistance to immunotherapy which might be intrinsic to the tumor cells or that may be influenced by their microenvironment [13]. This paper reviews ongoing clinical trials of ICIs in HCC patients
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