WCLC 2025 - Posters & ePosters-PT1.03.01 Precision Medicine Platform to Guide the Treatment of NSCLC

Pdf Summary

The Precision Medicine Platform (PMP) developed by the University of Michigan and the Judith Tam ALK Lung Cancer Research Initiative is designed to guide personalized treatment of Non-Small Cell Lung Cancer (NSCLC). This platform integrates patient-derived organoids (PDOs) and xenograft models (PDX) with comprehensive genomic, transcriptomic, and clinical data to enable rapid ex vivo drug screening and in vivo validation. By combining molecular profiling with functional drug testing, PMP aims to accurately predict individual patient drug responses, uncover mechanisms of drug sensitivity and resistance, and inform clinical decision-making.<br /><br />PMP was tested on NSCLC samples, particularly focusing on ALK-rearranged tumors. The platform demonstrated assay reproducibility across biopsy types such as pleural effusion and paracentesis samples, supporting its reliability even with limited tissue availability. Screening of 11 ALK+ PDOs revealed varied sensitivity to different ALK inhibitors, reflecting patient-specific therapeutic responses and resistance patterns. This heterogeneity underscores the importance of personalized therapy guided by functional assessment.<br /><br />Comprehensive genomic profiling of PDOs revealed a spectrum of driver and passenger mutations, with diverse pathogenic variants across patients, further illustrating tumor molecular heterogeneity. Integration of multiomic data with drug sensitivity results enabled generation of actionable, ranked drug lists per patient, enhancing the precision of treatment recommendations.<br /><br />The platform’s strong negative predictive value allows exclusion of ineffective therapies, sparing patients from unnecessary toxicity and optimizing clinical outcomes. By recapitulating resistance mechanisms observed in patients, PMP serves as a robust preclinical tool for studying drug resistance and testing novel combination therapies.<br /><br />In conclusion, this precision medicine approach facilitates rapid, patient-specific drug testing from small biopsy samples, supports broader inclusion in studies, and provides a reliable, data-driven basis for personalized NSCLC therapy selection.

Asset Subtitle

Sofia Merajver

Meta Tag

Speaker Sofia Merajver

Topic Tumor Biology – Translational Biology

Keywords

Precision Medicine Platform

Non-Small Cell Lung Cancer

Patient-Derived Organoids

Xenograft Models

Genomic Profiling

ALK-Rearranged Tumors

Drug Sensitivity Testing

Personalized Therapy

Multiomic Data Integration

Drug Resistance Mechanisms