Identification of novel small molecule inhibitors of ETS transcription factors

TL;DR

This paper introduces a new method to find small molecules that can inhibit ETS transcription factors, which are linked to cancer growth and spread.

Contribution

The study provides a proof-of-principle framework for identifying novel inhibitors of ETS transcription factors using high-throughput screening.

Findings

High-throughput screens identified candidate small molecule inhibitors of ETS transcription factors.

The approach could lead to new therapeutic strategies for targeting cancer growth and angiogenesis.

Abstract

The evolutionarily conserved E‐Twenty‐Six (ETS) family of transcription factors acts downstream of major signal transduction pathways and plays a pivotal role in tissue development and maintenance. Importantly, their function is frequently corrupted in a substantial proportion of tumour types, and they are also indispensable for angiogenic sprouting, a hallmark of cancer, which is essential for fuelling tumour enlargement and dissemination. Consequently, targeting aberrant ETS activity could potentially represent a precise and effective means by which to block tumour growth. Here, we present proof‐of‐principle high‐throughput screens and an initial characterization of candidate hits, as a methodological and conceptual framework for the identification of novel ETS transcription factor inhibitors, which may ultimately lead to new therapeutic avenues for treating cancer.

ETS transcription factors play an essential role in tumourigenesis and are indispensable for sprouting angiogenesis, a hallmark of cancer, which fuels tumour expansion and dissemination. Thus, targeting ETS transcription factor function could represent an effective, multifaceted strategy to block tumour growth.

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