Developing targeted therapeutics for hepatocellular carcinoma: a critical assessment of promising phase II agents

ABSTRACT

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the first for primary liver tumors. In recent years greater therapeutic advancement was represented by employment of tyrosine kinase inhibitors (TKIs) either in monotherapy or in combination with immune checkpoint inhibitors (ICIs).

Areas covered

Major attention was given to target therapies in the last couple of years, especially in those currently under phase II trials. Priority was given either to combinations of novel ICI and TKIs or those targeting alternative mutations of major carcinogenic pathways.

Expert opinion

As TKIs are playing a more crucial role in HCC therapeutic strategies, it is fundamental to further expand molecular testing and monitoring of acquired resistances. Despite the recent advancement in both laboratory and clinical studies, further research is necessary to face the discrepancy in clinical practice.

KEYWORDS:

• HCC
• phase II trials
• precision medicine
• target therapy
• TKI

Article highlights

• Hepatocellular carcinoma (HCC) is the 6th most common primary neoplasm worldwide.

• Greater interest was given to personalized therapies, in particular by targeting molecules involved in major HCC pathways (e.g. VEGF-dependent angiogenesis, Wnt-beta catenin pathway, Ras- Raf- ERK1/2MAPK and PI3K-Akt pathways).

• Promising phase II trials are under development studying new tyrosine kinase inhibitors (TKIs) either in monotherapy or in combination with immune checkpoint inhibitors (ICI).

• Many challenges are still yet to be overcome due to great HCC heterogeneity and evolution.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed they receive remuneration from Eisai Co., Ltd. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.