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 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.

T.P.C. is a ThermoFisher Scientific, Inc SAB member and receives research funding from AbbVie. E.F.P. is a SAB member and consultant to Ignite Proteomics, Inc., and receives research funding from Genentech, Pfizer, Mirati, Springworks Therapeutics, Deciphera, AbbVie, and is a co-inventor of the RPPA technology described herein, and related HER2 biomarker patents and receives royalties on the related license agreements. K.N. is an independent consultant and receives funding from Catalyst Medical Media, Clinical Care Options, Global Healthcare Marketing & Communications, Health and Wellness Partners, Interactive Forums, MphaR, and PharMecha. J.D, B.C., and C.M are full-time employees of Ignite Proteomics, Inc.

This work was supported, in part, by a generous contribution from the Win Sheridan family funds.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

From October 2021 to December 2023, a total of 174 adult (≥18 years of age) patients with advanced solid tumor malignancies seeking treatment were consented and enrolled under a Western IRB-approved protocol into the Inova Schar Cancer Institute Molecular Tumor Board (MTB) study (protocol number U20-19-4308). The written informed consents included the provision to analyze and publish information and data regarding the patients clinical presentation, and results and data from precision medicine/next generation genomic sequencing testing, including the RPPA profiling data. Eligible patients had pathology-confirmed cancer by tumor biopsy and had tumor available for testing. Patients with multiple concurrent malignancies were eligible. Patients had received varied lines of previous therapy, ranging from treatment-naive to heavily pre-treated. All experimental protocols involving human data in this study were in accordance with the Declaration of Helsinki and written informed consent was obtained from all patients.

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The NGS data that support the findings of this study were generated by Tempus Labs, Inc. but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are available from the authors upon reasonable request and with the permission of Tempus Labs, Inc.