Pleural mesothelioma: a snapshot of emerging drug targets and opportunities for non-surgical therapeutic advancement

ABSTRACT

Introduction

Pleural mesothelioma is a rare and aggressive cancer originating in the pleura, with a devastating prognosis and limited treatment options. There have been significant advancements in the management of this disease in recent years. Since 2021, nivolumab and ipilimumab immune checkpoint inhibitors have become the new standard of care for first-line treatment of pleural mesothelioma.

Areas covered

While a combination of chemotherapy and immune checkpoint inhibitors appears to be the next step, targeted therapies are emerging thanks to our understanding of the oncogenesis of pleural mesothelioma. Moreover, several new strategies are currently being investigated, including viral therapy, antibody-drug conjugates, and even cell therapies with CAR-T cells or dendritic cells. In this review, we will explore the various future opportunities that could potentially transform patients’ lives in light of the clinical trials that have been conducted.

Expert opinion

Future clinical studies aim to rebiopsy patients after disease progression to identify new molecular alterations and to be associated with ancillary studies, guiding subsequent therapy decisions. Predicting and investigating treatment resistance mechanisms will lead to innovative approaches and improved treatment outcomes.

KEYWORDS:

• Pleural mesothelioma
• innovative therapeutics
• Personalized medicine
• immunotherapy
• targeted therapy
• cell therapy
• oncovirotherapy

Article highlights

• Double immunotherapy (anti-PD1 and anti-CTLA4) is the standard of care in first-line setting but the association with chemotherapy will soon probably be the next step as in non-small cell lung cancer.

• New intra-pleural treatments have been tested using oncovirotherapies and CAR-T cell therapies and seem to be effective.

• Personalized therapies have been evaluated using tumor cell vulnerabilities which are promising.

• Targeting pleural mesothelioma with antibodies (specific or drug conjugate) needs further development.

• The future relies on the combination of these new innovative treatments with immunotherapy in order to improve their efficacy or to use them as a second-line treatment.

• Relevant preclinical models will identify new treatments, and rebiopsy and ancillary studies will provide new insights in the resistance mechanisms of the tumor to different treatments.

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

Acknowledgments

Figures were partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported licence and https://bioicons.com/.

Additional information

Funding

This work was supported by Inserm. JBA benefits from a [PhD grant] from Fondation pour la Recherche Medicale (JBA).