Grant Number:	1R01CA314931-01 Interpret this number
Primary Investigator:	Lee, Hyun-Sung
Organization:	Baylor College Of Medicine
Project Title:	Liquid Multiomics for Personalized Systemic Treatment in Malignant Pleural Mesothelioma
Fiscal Year:	2026

PROJECT SUMMARY / ABSTRACT Malignant pleural mesothelioma (MPM) presents a significant challenge in oncology due to its rarity, lethality, and heterogeneity. This complexity necessitates the development of innovative therapeutic strategies, particularly in light of the partial effectiveness and resistance issues associated with current immune checkpoint inhibitors (ICIs). Our research addresses these challenges by focusing on the identification and validation of liquid biomarkers to enable personalized treatment strategies and improve patient outcomes in MPM. Recent advancements in ICIs have offered new hope, with monotherapy showing about a 20% objective response rate, which can be significantly improved with combination therapies. However, resistance to these treatments remains a substantial barrier, affecting approximately two-thirds of MPM patients. We have identified key prognostic factors such as tumor PD-L1 expression, which is associated with unfavorable survival after conventional treatment without ICIs, and the beneficial impact of tertiary lymphoid structures, immune triads, intact 9p21.3 loci, and low soluble mesothelin-related peptide (SMRP) levels on ICI response. We propose a dual-aim research strategy to address the urgent need for precise biomarkers in MPM treatment. Aim 1 focuses on validating the combined utility of MHC genotype and SMRP levels to stratify patient survival and monitor disease progression, employing a predictive model validated through a cohort of over 400 MPM patients. Aim 2 seeks to elucidate the mechanistic connections between liquid multiomics profiles and the tumor immune landscape, using state-of-the-art technologies to identify and verify novel biomarkers and therapeutic targets. This integrative analysis of immune genotyping and circulating proteins aims to accurately map the tumor immune landscape, guiding the development of biomarker-driven therapeutic strategies. By leveraging liquid multiomics for molecular profiling, our project stands to significantly deepen the understanding of MPM biology, identify clinical-grade liquid biomarkers for treatment response prediction, and advance precision oncology. Our multidisciplinary team, with expertise spanning basic to translational research and advanced immunology, is uniquely positioned to make impactful contributions to precision cancer therapy for MPM. This research promises not only to enhance the precision and efficacy of MPM care but also to set new standards in the management of this challenging disease, marking a significant step forward in the pursuit of personalized oncology solutions.





None