Product Launch: IsoPlexis’ Intracellular Signaling Omics Characterizes Signaling Mechanisms Driving Resistance

  • IsoPlexis’ Single-Cell Intracellular Proteome and Single-Cell Metabolome solutions for intracellular signaling omics provide functional characterization of the signaling networks and resistance pathways of cancer cells, for the development of improved treatments to combat therapeutic resistance.
  • Many factors can drive drug resistance in tumors, including changes in tumor microenvironment, tumor size, and mutation rate. Because tumor cells are heterogenous, IsoPlexis’ ability to profile the function of each single cell is crucial to the treatment and prevention of therapeutic resistance.
  • In a study published in Nature Communications, researchers Su, et al. used IsoPlexis’ Single-Cell Intracellular Proteome solution for intracellular signaling omics to analyze the resistance pathways of BRAFV600E M397 mutant melanoma cells treated with BRAF inhibitor (BRAFi). IsoPlexis’ technology revealed two distinct subpopulations of BRAFV600E M397 cells which followed different pathways to drug resistance and had different drug susceptibilities. IsoPlexis’ technology provided insights for researchers to identify effective combination therapies to combat this resistance.

IsoPlexis Fills the Gap in Understanding of Treatment Resistant Cancer Cell States

Over the past decades, researchers and clinicians have worked tirelessly to develop and administer effective targeted cancer therapies, improving prognosis and long-term survival in many cancers. However, while these therapies can certainly be effective, cancer cells are prone developing treatment-resistance. Techniques such as genomics have been unable to identify and predict the development of resistance, as mechanisms of resistance are often due to functional adaptation and not a genomic change. IsoPlexis’ intracellular signaling omics fills this knowledge gap, allowing researchers to identify resistance pathways and develop individualized treatment regiments to combat therapeutic resistance.

In the Cancer Cell commentary, “Kicking Genomic Profiling to the Curb,” IsoPlexis’ technology was highlighted for its ability to reveal “re-wiring of critical signaling nodes as the mechanisms of resistance” and “assay up to 35-40 proteins.”1 With IsoPlexis’ intracellular signaling omics, researchers can identify functional pathways driving therapeutic resistance and develop combination therapies to combat resistant cell states and resolve tumor heterogeneity.

The Single-Cell Intracellular Proteome and Single-Cell Metabolome solutions identify polyfunctional cell subsets to provide a comprehensive picture  of altered signal transduction networks in tumors, which allow researchers to identify whether therapies targeting protein signaling networks are effective. With these solutions on the automated IsoLight platform, researchers can push forward the treatment of complex cancers and identify therapies which target or circumvent resistance pathways.

Due to the heterogeneity of tumor cells, IsoPlexis’ ability to provide intracellular signaling omics on the single-cell level is critical. Like tumor cells themselves, the factors which can drive therapeutic resistance in cancers are varied. Tumors can present with either innate resistance, in which treatment resistant cells are present in the tumor before treatment, or developed resistance. Factors such as tumor size, mutation rate, changes in genome and tumor microenvironment, and pathway alterations can all contribute to or drive treatment resistance.

Drug Resistance in Cancer Therapy

IsoPlexis’ Intracellular Signaling Omics Identifies Functional Signaling Mechanisms and Previously Undetected Sources of Resistance in Rare Cells

In a study published in Nature Communications, researchers Su, et al. utilized IsoPlexis’ technology for intracellular signaling omics to analyze the resistance pathways of BRAFV600E M397 mutant melanoma cells treated with BRAF inhibitor (BRAFi) over five days. IsoPlexis’ solutions provided functional characterization of various aspects of the BRAFV600E M397 cells, including phosphoproteins and metabolites, oncogenic signaling, and proliferation.2 Importantly, the platform also revealed two distinct subpopulations of cells which followed different pathways to drug resistance. Su, et al. were able to identify drug susceptibilities for each of these pathways. IsoPlexis’ intracellular signaling omics provided the insights for researchers to identify combination therapies to combat this resistance that were both effective and low in cytotoxicity.

IsoPlexis’ unique intracellular signaling omics allows researchers to attack cancer cell resistant states at their source using single-cell functional data for a comprehensive understanding of the signaling pathways driving resistance. To learn more about how IsoPlexis’ Single-Cell Intracellular Proteome and solution maps proteomic pathways at the single cell level to aid scientific discoveries, download our eBook.

References:

  1. Lam FC, et al. Kicking Genomic Profiling to the Curb: How Re-wiring the Phosphoproteome Can Explain Treatment Resistance in Glioma. Cancer Cell 29: 435-436, 2016.
  2. Su Y, et al. Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line. Nature Communications 11: 2345, 2020.
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