Real-time functional proteomics enhances therapeutic targeting in precision oncology molecular tumor boards
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.
Authors
- Aratara Nutcharoen
- Justin Davis (ORCID: https://orcid.org/0000-0002-8153-5650)
- Allison L. Hunt (ORCID: https://orcid.org/0000-0002-2223-7944)
- Emanuel F. Petricoin (ORCID: https://orcid.org/0000-0001-9146-5572)
- Jamie Randall
- Tamara Abulez (ORCID: https://orcid.org/0000-0001-5325-5064)
- John F. Deeken (ORCID: https://orcid.org/0000-0001-8414-1553)
- MAHESH M. MANSUKHANI (ORCID: https://orcid.org/0000-0003-2044-0751)
- Amin Benyounes
- Claudius Mueller
- Kara Nyberg
- Timothy Lewis Cannon (ORCID: https://orcid.org/0000-0001-5033-3071)
- Laura Johnston
- Brian Corgiat (ORCID: https://orcid.org/0000-0002-7810-8500)
- Meenakshi Sharma (ORCID: https://orcid.org/0000-0002-9721-7104)
- Thomas P. Conrads (ORCID: https://orcid.org/0000-0003-4742-3281)
- Susan L. Melvin
- G. Larry Maxwell
- Whitney Rose Swain
- Nicholas W. Bateman
Institutions
- Inova Health System (US)
- Henry M. Jackson Foundation (US)
- George Mason University (US)
- Columbia University Irving Medical Center (US)
- Walter Reed National Military Medical Center (US)
- Inova Fairfax Hospital (US)
- CoorsTek (United States) (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-04-15
- DOI
- https://doi.org/10.1038/s41698-025-00868-y
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- U.S. Department of Defense
- Uniformed Services University of the Health Sciences
- U.S. Navy