Expression proteomics reveals protein targets and highlights mechanisms of action of small molecule drugs

TL;DR

This study introduces a proteomics-based method to identify drug targets and mechanisms of action in cancer cells, streamlining the discovery process for anticancer drugs.

Contribution

The paper presents a novel proteomics approach that rapidly deconvolutes drug targets and mechanisms of action by analyzing protein abundance profiles across cell types.

Findings

Identified proteins with cell-type independent drug regulation.

Mapped drug targets onto known protein networks.

Provided signatures of cellular death and survival pathways.

Abstract

Phenomenological screening of small molecule libraries for anticancer activity yields potentially interesting candidate molecules, with a bottleneck in the determination of drug targets and the mechanism of anticancer action. A novel approach to drug target deconvolution compares the abundance profiles of proteins expressed in a panel of cells treated with different drugs, and identifies proteins with cell-type independent and drug-specific regulation that is exceptionally strong in relation to the other proteins. Mapping top candidates on known protein networks reveals the mechanism of drug action, while abundant proteins provide a signature of cellular death/survival pathways. The above approach can significantly shorten drug target identification, and thus facilitate the emergence of novel anticancer treatments.