Real-time functional proteomics enhances therapeutic targeting in precision oncology molecular tumor boards

Abstract Collaborative review of molecular profiling data by multidisciplinary molecular tumor boards (MTB) is increasingly important for improving patient management and outcomes, though currently relies nearly exclusively on nucleic acid next-generation sequencing (NGS) and limited panels of immun...

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Main Authors: Allison L. Hunt, Jamie Randall, Mahesh M. Mansukhani, Kara Nyberg, Aratara Nutcharoen, Justin Davis, Brian Corgiat, Claudius Mueller, Savannah Melvin, Meenakshi Sharma, Laura Johnston, Whitney Swain, Tamara Abulez, Nicholas W. Bateman, G. Larry Maxwell, John Deeken, Amin Benyounes, Emanuel F. Petricoin, Timothy L. Cannon, Thomas P. Conrads
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00868-y
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Summary:Abstract Collaborative review of molecular profiling data by multidisciplinary molecular tumor boards (MTB) is increasingly important for improving patient management and outcomes, though currently relies nearly exclusively on nucleic acid next-generation sequencing (NGS) and limited panels of immunohistochemistry-based protein abundance data. We examined the feasibility of incorporating real-time laser microdissection (LMD) enrichment of tumor epithelium and commercial CLIA-based reverse phase protein array (RPPA) protein drug target expression/activation profiling into our cancer center’s MTB to complement standard clinical NGS-based profiling. The LMD-RPPA workflow was performed within a therapeutically permissive timeframe with a median dwell time of nine days, during which specimens were processed outside of standard clinical workflows. The RPPA-generated data supported additional and/or alternative therapeutic considerations for 54% of profiled patients following review by the MTB. These findings suggest that integrating proteomic/phosphoproteomic and NGS-based genomic data creates opportunities to further personalize clinical decision-making for precision oncology.
ISSN:2397-768X