Epidermal growth factor receptor (EGFR)-targeted therapies in mesothelioma

ABSTRACT

Introduction

Malignant mesothelioma (MM) is an aggressive malignancy arising from the mesothelial cells lining the pleura and other serosal membranes. It is associated with an extremely poor prognosis and has limited therapeutic options.

Areas covered

Epidermal growth factor receptor (EGFR) is known to be highly overexpressed in mesothelioma with reported EGFR overexpression between 44 to 97%. Given this, several anti-EGFR agents have been trialed in mesothelioma. In this review, we provide an overview of the current available data on anti-EGFR therapies in MM and future directions of investigation with these targeted agents in MM.

Expert opinion

While many anti-EGFR therapies have failed to show significant efficacy in the management of MM, the pathway is biologically active and its abrogation preclinically points toward it being a valid target. Toward targeting the pathway, many novel EGFR-based therapies are still being investigated. Current ongoing research of interest in MM include EGFR-targeted nanotechnology approach for drug delivery, antibodies targeting the extracellular EGFR and potentially anti-EGFR antibody drug conjugates.

KEYWORDS:

• Epidermal growth factor receptor (EGFR)
• EGFR overexpression
• malignant mesothelioma
• targeted therapies

Article highlights

• EGFR is known to be highly overexpressed in malignant mesothelioma with reported expression between 44 and 97%.

• Despite promising preclinical data, many clinical trials investigating EGFR TKIs and EGFR targeting antibodies have yet to demonstrate significant clinical efficacy in patients with malignant mesothelioma, although some responses have been seen.

• New approaches including delivery of cytotoxic chemotherapy, or siRNA, linked to antibodies targeting EGFR-expressing malignant mesothelioma cells have shown initial promise in the clinic.

• CAR-T cell therapy targeting EGFR expressing cancers has also begun clinical trials and may have impact in malignant mesothelioma patients.

• Combination therapy targeting EGFR and other compensatory signaling pathways may have future impact in treatment of patients with malignant mesothelioma.

This box summarizes key points contained in the article.

Declaration of interest

PL Chia was supported by an International Association for the Study of Lung Cancer (IASLC) fellowship award, and is a recipient of a University of Melbourne, Australian Postgraduate Award (APA). AM Scott was supported by research grants from Cancer Council of Victoria, grant support from NHMRC (Program Grant No: 1092788; Senior Practitioner Fellowship No: 1084178), and research funding from Abbvie, Medimmune, EMD Serono. T John was supported by research grants from Cancer Council of Victoria and has received personal fees from Takeda, Astra Zeneca, BMS, Novartis, Roche, Pfizer, Boehringer, Ingelheim, and Ignyta.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.