Emerging therapies targeting growth factors in hepatocellular carcinoma

ABSTRACT

Introduction

Hepatocellular carcinoma (HCC) is a primary liver cancer that commonly arises in the background of chronic liver inflammation and/or cirrhosis. Chronic liver inflammation results in the production of different growth factors, remodeling of the microenvironment architecture into fibrosis, and eventually carcinogenesis. Overexpression of some growth factors has been associated with worse prognosis in patients with HCC. Targeted therapies against growth factors may disrupt cell signaling and the mechanisms that allow for cell survival (e.g. angiogenesis, proliferation, metastases).

Areas Covered

We herein review potential growth factor targets of HCC and the limited research that exists regarding targeted therapy of these ligands and their receptors. We performed an extensive literature search to investigate preclinical studies, clinical research, and clinical trials.

Expert Opinion

Systemic therapy for patients with HCC is continuing to evolve. Anti-angiogenic therapy holds the most promise among targeted therapy for growth factors among patients with HCC. Improving our understanding of growth factors in HCC will hopefully lead to the development of new targeted therapies and strategies for combination therapies with immune checkpoint inhibitors.

KEYWORDS:

• Hepatocellular carcinoma
• growth factors
• targeted therapy
• liver cancer
• anti-angiogenic therapy

Article highlights

• Hepatocellular carcinoma (HCC) is a primary liver cancer that commonly arises in the background of chronic liver inflammation and/or cirrhosis. Chronic liver inflammation results in the production of different growth factors, remodeling of the microenvironment architecture into fibrosis, and eventually carcinogenesis.

• Overexpression of some growth factors is associated with worse prognosis in patients with HCC. Targeted therapy against growth factors may disrupt cell signaling and the mechanisms that allow for cell survival (e.g. angiogenesis, proliferation, metastases).

• Potential growth factors include VEGF, PDGF, FGF, HGF, and angiopoietin/Tie2.

• Sorafenib was the first tyrosine kinase inhibitor to demonstrate efficacy for advanced HCC in the SHARP trial. More recently, bevacizumab (monoclonal antibody against VEGF) has become standard of care in combination with atezolizumab based on the IMbrave150 trial.

• Improving our understanding of growth factors in HCC will hopefully lead to the development of new targeted therapies and strategies for combination therapies with immune checkpoint inhibitors.

Declarations of interest

The authors have no 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

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.