190P - A large scale proteogenomics atlas for precision oncology research

Background

Recent advances in the field of mass spectrometry proteomics have led to a massive increase in the volume of high-quality publicly available proteomics datasets. This growth creates an underutilized resource with potential for new discoveries. Effectively utilizing this vast resource of clinical samples is a major challenge.

Methods

We utilize the growing availability of proteomics and post-translational modifications (PTMs) data for drug and biomarker discovery. The AIMS™ platform combines multi-omic data curated from the public domain, together with internally generated high quality proteomic and phosphoproteomic data. The platform incorporates diverse clinical annotations, tumor and normal samples, drug sensitivity, patient outcomes and relevant bioinformatic knowledge bases.

Results

Our comprehensive analysis incorporated 5,882 samples, including both tumor and normal adjacent tissues, collected from a variety of public and proprietary sources. We identified distinct pan-cancer clusters across four cancer types, uncovering more than 15 potential targets uniquely enriched within one cluster with a false discovery rate below 0.1. Additionally, our algorithm identified prognostic markers specific to lung cancer. This marker effectively stratifies patients into low- and high-risk groups for overall survival (OS), yielding a robust p-value of 7.2e-04. Moreover, our AIMS platform has identified a novel biomarker for MEK1 inhibitor response, associated with downstream BRAF signaling. This biomarker has shown significant improvement in Kaplan-Meier (KM) survival analyses (p value < 0.01) in Lung SCC, surpassing known mutation-based biomarkers.

Conclusions

Protai has forged a high quality, routinely updated, clinical atlas of cancer proteomics and PTMs. AIMS™ harmonization method is validated and evaluated with two separate benchmarks. Increased sample size translates into qualitative improvement, offering unique precision oncology insights including predictive and prognostic biomarker discovery, indication expansion and discovery of new therapeutic targets and combinations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Protai Bio.

Disclosure

T.A. Yap: Financial Interests, Personal, Other, Consultant: Almac, Aduro, AstraZeneca, Atrin, Axiom, Bayer, Bristol Myers Squibb, Clovis, Cybrexa, EMD Serono, Guidepoint, Ignyta, I-Mab, Jansen, Merck, Pfizer, Repare, Roche, Schrodinger, Varian, Zai Labs, AbbVie, Acrivon, Adagene, Amphista, Artios, Athena, Avoro, Baptist Health Systems, BeiGene, Boxer, C4 Therapeutics, Calithera, Cancer Research UK, Diffusion, F-Star, Genmab, Glenmark, GLG, Globe Life Sciences, GSK, Idience, ImmuneSensor, Institut Gustave Roussy, Intellisphere, Kyn, MEI Pharma, Mereo, Natera, Nexys, Novocure, OHSU, OncoSec, Ono Pharma, Pegascy, PER, Piper-Sandler, Prolynx, resTORbio, Theragnostics, Versant, Vibliome, Xinthera, ZielBio, Radiopharm Theranostics, Sanofi, Ellipses.Life, LRG1, Panangium, Pliant Therapeutics, Synthis, Tessellate Bio, TD2 Theragonostics, Tome Biosciences, Zentalis, Amgen Inc., Astex, Avenzo, BioCity Pharma, Blueprint, Carrick Therapeutics, Circle Pharma, Daiichi Sankyo, Dark Blue Therapeuticcs, Duke Street Bio, 858 Therapeutics, EcoR1 Capital, Entos, FoRx Therapeutics AG, Genesis Therapeutics, Ideaya Biosciences, Impact Therapeutics, Merit, Monte Rosa Therapeutics, Nested Therapeutics, Nimbus, Odyssey, Onxeo, Protai Bio, Ryvu Therapeutics, SAKK, Servier, Synnovation, Tango, TCG Crossover, Terremoto Biosciences, Terns Pharmaceuticals, Tolremo, Tome, Thryv Therapeutics, Trevarx Biomedical, Veeva, Voronoi Inc.; Financial Interests, Personal, Advisory Board: BridGene Biosciences, Debiopharm, Grey Wolf Therapeutics, Institut Gustave Roussy, Joint Scientific Committee for Phase I Trials in Hong Kong, Prelude Therapeutics; Financial Interests, Personal, Other, University of Texas MD Anderson Cancer Center, where I am Medical Director of the Institute for Applied Cancer Science, which has a commercial interest in DDR and other inhibitors (IACS30380/ART0380 was licensed to Artios): MD Anderson Cancer Center, Institute for Applied Cancer Sciences; Financial Interests, Personal, Stocks/Shares: Seagan; Financial Interests, Institutional, Other, Grant/Research support: Bayer, Cyteir, EMD Serono, GSK, Karyopharm, Pfizer, Repare, Sanofi, Artios, AstraZeneca, BeiGene, BioNTech, Blueprint, BMS, Clovis, Constellation, Eli Lilly, Forbius, F-Star, Genentech, Haihe, ImmuneSensor, Ionis, Ipsen, Jounce, KSQ, Kyowa, Merck, Mirati, Novartis, Ribon Therapeutics, Regeneron, Rubius, Scholar Rock, Seattle Genetics, Tesaro, Vivace, Acrivon, Zenith; Financial Interests, Institutional, Research Grant: Boundless Bio, Ideaya; Financial Interests, Institutional, Other, Grant/Research Support: Insilico Medicine, Tango; Financial Interests, Institutional, Local PI: CPRIT, Gilead, Golfers against Cancer, Exelixis, NIH/NCI, Pliant, Prelude, Roche, Synnovation, V Foundation, Zentalis. All other authors have declared no conflicts of interest.