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OncoHost's Plasma Proteomics Research Reveals Key Mechanisms of Immunotherapy Resistance in NSCLC

• OncoHost will present new research at AACR 2025 revealing five distinct proteomic expression patterns that explain resistance to immunotherapy in non-small cell lung cancer patients.

• The study identified 388 resistance-associated proteins (RAPs) with 17.5% potentially targetable by existing or investigational drugs, opening new avenues for personalized treatment strategies.

• This international collaborative research advances precision medicine by providing mechanistic insights into treatment resistance, potentially improving first-line immunotherapy decision-making for NSCLC patients.

OncoHost announced today that it will present groundbreaking research on plasma proteomics in non-small cell lung cancer (NSCLC) at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2025, scheduled for April 25-30 in Chicago, Illinois.
The research, detailed in a scientific poster titled "Clinical and biological implications of plasma proteomic patterns in NSCLC patients treated with immune checkpoint inhibitors," explores the proteomic foundations of the company's PROphetNSCLC™ treatment guidance tool. This innovative diagnostic approach aims to optimize first-line immunotherapy decisions for patients with advanced NSCLC.

Uncovering Mechanisms of Immunotherapy Resistance

The study represents a significant advancement in understanding why certain NSCLC patients fail to respond to immunotherapy treatments. By analyzing plasma samples, researchers identified 388 resistance-associated proteins (RAPs) that form the basis of the PROphetNSCLC™ model.
"This research provides a deeper understanding of the biological underpinnings driving resistance to immunotherapy in NSCLC," explained Dr. Michal Harel, Director of Science and Innovation at OncoHost and lead author of the study. "Our analysis of resistance-associated proteins identifies key proteomic signatures that not only explain clinical outcomes but can also help stratify patients and identify new therapeutic targets."
The investigation revealed five distinct expression patterns across three groups: healthy individuals, NSCLC patients who derived clinical benefit (CB) from immunotherapy, and those who experienced no clinical benefit (NCB). These patterns offer critical insights into the biological mechanisms of treatment resistance that can be monitored through plasma analysis.

Translational Implications for Precision Oncology

Perhaps most promising is the finding that 17.5% of the identified RAPs could potentially be targeted with existing or investigational drugs. This discovery suggests that these proteins may serve as novel intervention targets, potentially leading to more effective treatment strategies for patients who would otherwise not respond to standard immunotherapy approaches.
The research highlights several key biological processes involved in immunotherapy resistance, including angiogenesis, immune modulation, chemoresistance, and cell proliferation. By understanding these mechanisms, clinicians may soon have new tools to overcome treatment resistance in NSCLC patients.

International Collaborative Effort

The study represents a broad international collaboration between OncoHost and leading academic institutions and cancer centers, including The Ohio State University, UC Davis, Baylor University Medical Center, and Roswell Park Comprehensive Cancer Center, among others.
"Being selected to present at AACR reinforces the scientific and clinical relevance of our work," said Ofer Sharon, MD, CEO of OncoHost. "We are moving beyond predictive diagnostics into an era where understanding the 'why' behind treatment resistance is critical to driving real-world precision medicine. This study brings us closer to realizing the full potential of proteomics in oncology."

Clinical Application Through PROphetNSCLC™

The PROphetNSCLC™ test represents the practical application of this research, offering a blood-based diagnostic tool that requires only a single sample to guide immunotherapy decision-making. According to OncoHost, the test provides physicians with crucial guidance on optimal first-line immunotherapy treatment plans for individual patients, potentially improving overall survival outcomes.
The company's approach is supported by a large-scale prospective clinical trial involving over 40 sites and 1,700 patients worldwide, demonstrating OncoHost's commitment to robust clinical validation of its proteomics-based precision medicine platform.

Presentation Details

Dr. Michal Harel will present the poster on Monday, April 28, 2025, from 9:00 AM to 12:00 PM CDT during the "Predictive Biomarkers 3" session. The presentation will be available at Poster Board #27, and the abstract is currently accessible on the AACR website.
As immunotherapy continues to transform cancer treatment, understanding the mechanisms of resistance becomes increasingly crucial for optimizing patient outcomes. OncoHost's proteomics research represents an important step toward more personalized and effective cancer care, potentially benefiting thousands of NSCLC patients who might otherwise not respond to immunotherapy.
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