Predicting and Overcoming Resistance Using IsoPlexis’ Single-Cell Intracellular Proteomic and Metabolomic Analysis Tools

Abig difficulty in the field is that cancer cells establish resistance to targeted treatments, and scientists are striving to define and comprehend how these cancer cells are adjusting in response to these treatments. Cancer cells have been characterized at the hereditary and genomic levels, the practical mechanisms affecting protein-driven practical behaviors and activities can just be exposed through singlecell proteomics. Utilizing IsoPlexis proteomic barcoding technology, the scientists characterized cellular heterogeneity within cell populations at various timepoints and quantitatively linked numerous timepoints to characterize vibrant heterogeneity on an individual cell level. The IsoPlexis single-cell proteomics platform, the IsoLight, functions as a proteomic center that uncovers the true function from cancer and immune cells. IsoPlexis proteomics hub functionally phenotypes innate and adaptive immune cell populations and analyzes cell populations that shape the tumor microenvironment by looking at the secretome, intracellular proteome, and metabolome.

Abig difficulty in the field is that cancer cells develop resistance to targeted therapies, and researchers are aiming to comprehend and define how these cancer cells are adapting in reaction to these treatments. Cancer cells have been characterized at the genomic and genetic levels, the practical mechanisms affecting protein-driven practical habits and activities can only be exposed through singlecell proteomics.
Single-cell single-cell metabolomics and intracellular proteomics integrate to identify drug resistance in melanoma cells
The continuous adjustment of cancer cells presents a great challenge for developing drug-based treatments, as cells that at first react can rapidly adopt drug-resistant states. IsoPlexis single-cell proteomics and multiomic technologies can help define the systems and underlying elements driving drug resistance.
In a recent Nature Communications post, James Heaths group from the California Institute of Technology described using predictive single-cell intracellular proteomics and metabolomics to recognize how a cancer cell line shifts to a last drug-resistant state through 2 unique trajectories.1 When BRAFV600E mutant melanoma cells are treated with BRAF inhibitors, they rapidly become drug tolerant. To evaluate what was happening within these cells to produce a drug resistant state, Heaths team dealt with these mutant cells with the BRAF inhibitor vemurafenib for differing periods and evaluated them utilizing incorporated single-cell intracellular proteomics and metabolomics.
Using IsoPlexis proteomic barcoding technology, the researchers defined cellular heterogeneity within cell populations at different timepoints and quantitatively connected multiple timepoints to identify vibrant heterogeneity on an individual cell level. Cellular state changes ended up being popular around day 3, as a lot of penetrated analytes showed a temporal but sharp boost in difference. All of the metabolic enzymes and signaling phosphoproteins, all metabolic regulators except for one, and all resistant state markers and regulators except for one showed this phenomenon. This information showed Heaths team that cancer cell responses to a typical stimulus may involve multiple divergent functional pathways while still resulting in the exact same genomic phenotype. Comprehending these practical adjustments allowed the group to anticipate and develop a reliable restorative combination to overcome this adaptive resistance.
Revealing true function with the IsoLight proteomic hub
Proteomic analysis contributes in filling the knowledge space left by genomics, especially at the single-cell level. The IsoLight system from IsoPlexis makes it possible for scientists to determine real cellular functional phenotypes. Going beyond the limited info provided by cell surface area marker expression, IsoCode single-cell intracellular proteomic chips provide info on protein-protein interactions and pathway activation or deactivation, stressing modifications in protein expression and changes in phosphorylation profiles.
The IsoPlexis single-cell proteomics platform, the IsoLight, works as a proteomic center that discovers the true function from cancer and immune cells. IsoPlexis proteomics center functionally phenotypes natural and adaptive immune cell populations and analyzes cell populations that shape the growth microenvironment by looking at the secretome, intracellular proteome, and metabolome. The platform can recognizing approximately 32 various cytokines and intracellular proteins in a multiplexed way at the singlecell level. This is all integrated with IsoPlexis totally automated plug-and-play IsoSpeak software suite. This powerful software application analyzes information same day with instinctive and publication-ready sophisticated visualizations to assist researchers further accelerate their therapies.
See IsoPlexis.com to find out more on IsoPlexis intracellular proteome and metabolome technologies.
Referral
Y. Su et al., “Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a cancer malignancy cell line,” Nat Commun, 11:2345, 2020.
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