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

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

doi:10.1038/s41698-025-00868-y

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

NPJ Precis Oncol. 2025 Apr 15;9(1):111. doi: 10.1038/s41698-025-00868-y.

Authors

Allison L Hunt^{1

2}, Jamie Randall³, Mahesh M Mansukhani⁴, Kara Nyberg³, Aratara Nutcharoen^{3

5}, Justin Davis⁶, Brian Corgiat⁶, Claudius Mueller⁶, Savannah Melvin³, Meenakshi Sharma³, Laura Johnston³, Whitney Swain³, Tamara Abulez^{2

7}, Nicholas W Bateman^{2

7}, G Larry Maxwell^{1

2}, John Deeken³, Amin Benyounes³, Emanuel F Petricoin^{6

8}, Timothy L Cannon⁹, Thomas P Conrads^{10

11}

Affiliations

¹ Women's Health Integrated Research Center, Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA, 22003, USA.
² Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
³ Inova Schar Cancer Institute, Inova Health System, 8081 Innovation Park Drive, Fairfax, VA, 22031, USA.
⁴ Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 W 168th Street, New York, NY, 10032, USA.
⁵ Department of Pathology, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA.
⁶ Ignite Proteomics Inc., 15000 W 6th Avenue, Golden, CO, 80401, USA.
⁷ The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
⁸ Center for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA, 20110, USA.
⁹ Inova Schar Cancer Institute, Inova Health System, 8081 Innovation Park Drive, Fairfax, VA, 22031, USA. Timothy.Cannon@inova.org.
¹⁰ Women's Health Integrated Research Center, Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA, 22003, USA. conrads@whirc.org.
¹¹ Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA. conrads@whirc.org.

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.