Hepatocellular carcinoma, novel therapies on the horizon

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with high mortality rate. Incidence remains high due to the persistent prevalence of viral hepatitis, alcoholic cirrhosis, and non-alcoholic fatty liver disease (NFLD). Despite screening efforts, the majority of patients present with advanced disease, add to the high risk of recurrence after curative surgery. Conventional chemotherapy did not alter the nature history of advanced and metastatic HCC. The discovery of multiple tyrosine kinase inhibitors (TKIs) led to the approval of sorafenib as first efficacious therapy. A new era in the treatment paradigm of HCC is evolving. Since the advent of sorafenib as an active treatment option for patients presenting with advanced or metastatic disease, several agents have been examined. This was linked with many failures, and success stories to celebrate. Herein, we describe the historical progress and current advances of systemic therapies post-sorafenib. Lenvatinib, regorafenib, cabozantinib, ramucirumab, pembrolizumab, and nivolumab, are all presently added and available therapeutic options in the advanced setting. The evaluation of novel treatment combinations including anti-angiogenic, TKIs plus checkpoint inhibitors, add to dual checkpoint inhibitors is evolving rapidly starting with the advent of the combination of atezolizumab plus bevacizumab. Combining local and systemic therapies is being actively investigated, as an option for locally advanced disease conventionally treated with locoregional approaches. The horizon remains promising and continues to evolve for HCC a disease long considered with unmet needs.

Non-alcoholic steatohepatitis and risk of hepatocellular carcinoma

“…Nivolumab [ 162 ] on the other hand, belongs to the novel immunotherapy category, with an overall response rate of 20%, currently in phase III clinical trial, performing significantly better than sofenib. [ 163 , 164 ]…”

Current perspectives on exosomes in the diagnosis and treatment of hepatocellular carcinoma (review)

“…95 Recently, several potential molecular targets (such as PD-1/PD-L1, cytotoxic T lymphocyte antigen 4 (CTLA-4), vascular endothelial growth factor (VEGF) pathway, tumor suppressor p53, skin cell adhesion molecule (EpCAM), and Wnt/β-Catenin) and therapeutics (such as nivolumab, pembrolizumab, and lenvatinib) have been widely used for the clinical treatment of HCC. [95][96][97] However, most target molecules for HCC exhibit poor clinical performance. Approximately 25% of HCC cases exhibit resistance to the currently used drugs.…”

Management of hepatocellular carcinoma

“…Combinations of ICIs targeting the programmed cell death-1 (PD-1) pathway and anti-angiogenic therapy have become the mainstream of combination therapy trials for HCC [32], [33,34]. A combination of atezolizumab and bevacizumab was the first treatment shown to improve the benefit of Sorafenib [35].…”