Advances in immunotherapy for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a prevalent disease with a progression that is modulated by the immune system. Systemic therapy is used in the advanced stage and until 2017 consisted only of antiangiogenic tyrosine kinase inhibitors (TKIs). Immunotherapy with checkpoint inhibitors has shown strong anti-tumour activity in a subset of patients and the combination of the anti-PDL1 antibody atezolizumab and the VEGF-neutralizing antibody bevacizumab has or will soon become the standard of care as a first-line therapy for HCC, whereas the anti-PD1 agents nivolumab and pembrolizumab are used after TKIs in several regions. Other immune strategies such as adoptive T-cell transfer, vaccination or virotherapy have not yet demonstrated consistent clinical activity. Major unmet challenges in HCC checkpoint immunotherapy are the discovery and validation of predictive biomarkers, advancing treatment to earlier stages of the disease, applying the treatment to patients with liver dysfunction and the discovery of more effective combinatorial or sequential approaches. Combinations with other systemic or local treatments are perceived as the most promising opportunities in HCC and some are already under evaluation in large-scale clinical trials. This Review provides up-to-date information on the best use of currently available immunotherapies in HCC and the therapeutic strategies under development.

The Landscape of lncRNAs in Hepatocellular Carcinoma: A Translational Perspective

“…However, in the case of HCC, some of those lncRNAs seem to confer a fitness advantage to cancer cells, offering a unique opportunity to expand the repertoire of potential targets. This is essential for HCC that activates several undruggable pathways [ 121 ] and where novel therapies have shown potent responses but only in a fraction of patients [ 164 ]. HCC patients could benefit from the additive or synergistic effects of co-targeting with novel first-line treatments and potentially useful lncRNA-based drugs.…”

Advances in Targeting Cutaneous Melanoma

“…Moreover, recently a landmark phase III randomized clinical study in which patients with unresectable hepatocellular carcinoma were treated with a PD-L1 inhibitor (atezolizumab) and a VEGF inhibitor (bevacizumab) combination found a significantly improved overall and progression-free survival when compared to a group treated with the standard of care protein kinase inhibitor, sorafenib [34]. Combinations of ICI with systemic and local treatments for HCC are already under evaluation in large-scale clinical trials, and atezolizumab/bevacizumab combinations are predicted to soon become the standard of care as first-line therapy in HCC [111].…”

Liquid Biopsy in Hepatocellular Carcinoma: Opportunities and Challenges for Immunotherapy

“…After years of sorafenib predominance and desolated perspectives, the skyline of systemic therapies for unresectable advanced HCC has considerably grown in the last decade. Not only more angiogenesis-and proliferation pathway-directed targeted therapies are available (TKIs; monoclonal antibodies), covering the therapeutic scenario from the first-to the third-line of treatment [109], but also ICIs are now well-established active agents and are gaining growing attention in the context of liver cancer [5]. Immuno-oncology (IO) represents a major breakthrough in this context, leading to a significant increase in median overall survival (OS) and to the possibility of long-term survival [110].…”

“…For advanced HCC, as for a few other solid cancers, immunotherapy is one of the most promising and novel treatment approaches. A number of ongoing clinical trials have been reported [2,5] in which various immunotherapies, such as immune checkpoint inhibitors (ICIs), are utilized for the treatment of HCC, either alone or in combination with targeted and/or systemic therapies [2,5].…”