The past, present, and future of targeted therapeutic approaches in patients with diffuse pleural mesotheliomas

Area of Science:

• Oncology
• Genomics
• Translational Medicine

Background:

• Diffuse pleural mesothelioma (DPM) is a rare cancer with a poor prognosis.
• Understanding the genomic landscape of DPM has advanced, but targeted therapies remain challenging.
• Current treatment options for DPM are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

• To review targeted therapeutic strategies for DPM currently under clinical investigation.
• To summarize key molecular targets being explored in DPM clinical trials.
• To identify challenges and future directions for developing effective DPM therapies.

Main Methods:

• Literature review of recent and ongoing clinical trials for DPM targeted therapies.
• Focus on specific molecular targets including VEGF, mesothelin, BRCA1-associated protein 1, WT1, NF2/YAP/TAZ, CDKN2, MTAP, VISTA, and ASS1.
• Analysis of preclinical data and clinical trial outcomes for these targets.

Main Results:

• Several molecular targets are being explored in DPM, with promising preclinical data.
• Clinical translation of targeted therapies has shown limited success in benefiting patients.
• Challenges include the lack of faithful preclinical models and effective biomarkers.

Conclusions:

• Despite promising preclinical research, targeted therapies for DPM have not yet yielded significant clinical benefits.
• Future efforts must focus on improving preclinical models that mimic DPM biology.
• Development of clinically relevant biomarkers and refined patient selection are crucial for advancing DPM treatment.