Single-Cell Signaling Analysis for Improved Targeted Therapies in Oncology

In cancer, adaptive drug resistance is driven by coordinated signaling pathway activations. Traditional technologies, like western blot, average protein information across every cell, thus the detection of rare, highly phosphoproteomically active cancer cells is missed. PhosphoFlow and other single-cell technologies can be limited in their multiplexing capabilities, which is required to reveal these key signaling pathways. Understanding signaling coordination through single-cell analysis of the phosphoproteome is critical for identifying early pathway activation in rare subsets of superpowered tumor cells driving resistance. IsoPlexis’ award-winning Single-Cell Signaling Solution uniquely coordinates proteomic signals directly from each cell, across thousands of single cells in parallel, to detect the most important activation pathways from supercharged cells. What distinguishes IsoPlexis’ platform from traditional technologies is the Single-Cell Signaling solution’s ability to quantify and highly multiplex 15+ analytes simultaneously from each cell. By detecting these critical activation pathways in rare cells and cell subsets, researchers can identify novel insights to help researchers “rewire” the phosphoproteome to fight diseases like cancer.

IsoPlexis’ Single-Cell Signaling Platform Predicts Success of Combination Therapy

Glioblastoma (GBM) is a highly lethal malignancy of the brain. In a paper published in Cancer Cell, researchers used IsoPlexis’ Single-Cell Signaling technology to overcome GBM drug resistance in a novel targeted combination therapy. In this study, IsoPlexis’ Single-Cell Signaling platform identified changes in signaling nodes missed by genomic analysis and western blot. Specifically, mTOR, ERK, and SRC pathways were detected and targeted, leading to sustained tumor suppression in vivo. The Single-Cell Signaling solution was able to provide clinically actionable insights into designing combination therapy strategies for more effectively treating GBM patients. This approach may allow researchers to identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations.

Revealing Independent Trajectories to Drug Tolerance with Single-Cell Signaling

In a separate study published in Nature Communications, researchers used IsoPlexis’ single-cell signaling platform to reveal independent trajectories of drug tolerance in mutant melanoma cells (BRAFV600E M397) treated with BRAF inhibitor (BRAFi) over five days. Researchers characterized phosphoproteins of single cells and measured oncogenic signaling coordination to reveal two different cell populations which took different, independently druggable paths to resistance. IsoPlexis’ unique ability to reveal early adaptive resistance pathways through the detection of coordinated signals “provides a potentially powerful methodology for predicting effective therapeutic combinations” to prevent and combat drug resistance in patients.

Clinical Insights Are Accelerated By Single-Cell Analysis

These high impact studies demonstrate the application of single-cell phosphoproteomics; a powerful approach that helps researchers better characterize cancer therapies and identify potential biomarkers that lead to new druggable targets.

The Single-Cell Signaling solution provides a simple, integrated solution for functionally characterizing signaling networks and resistance pathways of cancer cells for the development of improved treatments to combat therapeutic resistance. IsoPlexis’ proteomic barcoding technology allows for highly multiplexed analysis of  phosphoproteomic reactions, targeting up to 1,500 single cells per chip. Coordinating signaling networks of rare tumor cells enables researchers to characterize the effects of highly active, phosphoproteomically driven pathways, missed by traditional technologies, to support the advancement of more comprehensive treatments for cancer.

 

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