# Clinical Importance of Molecular Biomarkers in Pleural Mesothelioma

## TL;DR

This review explores how molecular biomarkers can help personalize treatment for pleural mesothelioma, a rare and aggressive cancer linked to asbestos exposure.

## Contribution

The paper highlights the potential of dynamic biomarkers and genomic alterations for guiding treatment and improving outcomes in mesothelioma.

## Key findings

- PD-L1 and TMB show inconsistent predictive value in mesothelioma and are not widely used in clinical decisions.
- Circulating tumor DNA and minimal residual disease detection are emerging tools for monitoring treatment response.
- Genomic alterations like MTAP, BAP1, CDKN2A, and NF2/YAP/TEAD offer potential targets for new therapies.

## Abstract

Pleural mesothelioma is a rare and aggressive cancer involving the lining of the lung, called the pleura, and is often associated with exposure to asbestos. This cancer is difficult to treat, and survival remains poor despite the recent development of new treatments. Current treatments include surgery, radiation, chemotherapy, immunotherapy, targeted therapy, and combinations of these modalities. At this time, it is difficult to know upfront which patients will benefit from which treatments. It is important to develop tools that can predict which patients may benefit from certain treatments and how to tailor these treatments over time. This review discusses the existing data on promising new tools to help guide personalized treatment approaches with the goal of improving outcomes for patients with mesothelioma.

Pleural mesothelioma (PM) is a rare malignancy with opportunities for improvement in current treatment paradigms despite recent advances in systemic therapy. While histology remains the most clinically relevant prognostic indicator, the expanding use of immunotherapy and ongoing clinical trials involving targeted therapies have increased interest in the development of predictive and prognostic biomarkers in this disease. This review summarizes the current biologic and therapeutic landscape of PM and the biomarkers that influence prognosis and treatment response. Biomarkers such as programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) demonstrate inconsistent predictive value in PM and are not currently used in clinical decision pathways in the real-world setting. This review highlights the developing role of dynamic biomarkers such as circulating tumor DNA (ctDNA) for molecular response assessment and minimal residual disease (MRD) detection. This review also examines important genomic and transcriptomic alterations in PM, such as MTAP, BAP1, CDKN2A, and NF2/YAP/TEAD. These alterations provide potential targets for ongoing early-phase clinical trials. Future advances in PM will depend on the development and integration of comprehensive biomarker models that combine clinicopathologic, immune, and molecular features of this complex and heterogenous disease.