Follow the Data: Make decisions to predict resistance to targeted inhibitor therapeutics in oncology1

Research Area: Solid tumor & oncology

Development Stage: Discovery

Goal: Discovering improved metrics to predict resistance to targeted inhibitor therapeutics in oncology

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How our single-cell systems are making a difference

Solution: The SNAI (signaling network activity index) and IsoPlexis’ systems provides insights into how BRAF mutant melanoma cells adapt to MAPK inhibition, that result in drug-tolerant or drug-resistant cell states, which can then be reversed.

Finding: A multiplexed set of functional proteins, analyzed at the single-cell level, pointed to signaling network hubs that drive the initiation of the melanoma cell adaptive transition. Targeting those hubs halted the transition and arrested resistance development.

Follow the data

The overall activity of the signaling network in each cancer cell may be quantified by the signaling network activity index (SNAI), which accounts for both the numbers and the strengths of statistically significant correlations.

The SNAI is highest at day 6, with particularly strong signaling participation of p-ERK and p-NFκB p65.1

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IsoPlexis finds critical differences

These results suggest a potential gain of function through MEK/ERK and NFκB p65 signaling that might lead to BRAFi drug tolerance by promoting the adaptive transition.

This behavior suggests that combining BRAFi with MEK and NFκB p65 inhibition might arrest the adaptive cell state transition toward drug-resistant phenotypes.1