A new therapeutic for sarcomas

Sarcomas are cancers of mesenchymal origin and are notoriously hard to treat: over the last twenty years, patients have not seen a single new therapy outside of traditional chemotherapy. Recent work has demonstrated that activation of a new pathway called ferroptosis can lead to cell death specifically in cancers. However, little is known about ferroptosis and new mediators of this pathway.

With our functional genomics platform, we identified a new RNA biomarker of ferroptosis. We then leveraged this RNA biomarker to screen thousands of small molecules for selective induction of ferroptosis in sarcoma cell lines. In less than a year, we’ve identified a lead compound with sub-100nM cellular EC50 in a fibrosarcoma model.

Target discovery in non-canonical forms of cell death

The genome is a dynamical system: each gene turns on and off at specific times following inhibition or activation of a signaling cascade. Understanding the causal drivers of signaling cascades dysregulated in disease can lead to new therapeutic targets for cancer, autoimmune, and neurological indications.

At Arpeggio, we are taking our functional genomics platform to look for new ways to selectively induce cell death in cancer. Our software and machine learning can take our functional genomics data, reconstruct the regulatory network of a cell, and perform in silico knockout experiments. This has dramatically increased our ability to prioritize new targets for validation studies in our lab.

with Arpeggio

Arpeggio is a team of leading experts in disease biology and drug discovery research. Our pipeline of unique small-molecule inhibitors were designed to probe biology on a systems level, getting to the heart of disease sooner.

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