Dynamic proteomics for investigating the response of individual cancer cells under drug action

Abstract

Evaluation of: Cohen AA, Geva-Zatorsky N, Eden E et al. Dynamic proteomics of individual cancer cells in response to a drug. Science 322(5907), 1511-1516 (2008). One of the greatest challenges in cancer chemotherapy is that seemingly identical cancer cells can respond differently to drug treatment. The pioneering work reported by Cohen and colleagues moves one step closer to solving this challenge. They develop a dynamic proteomics approach that utilizes fluorescent markers and a time-lapse microscope to detect the fluctuating locations and levels of approximately 1000 proteins in individual cancer cells at high temporal resolution. After adminstration of the cancer drug camptothecin, certain proteins display similar spatiotemporal distribution patterns in individual cells; for example, the drug target topoisomerase-1 shows a rapid decrease in protein level and in nuclear location. However, two particular proteins demonstrate cell-cell variability in their behavior corresponding to cell fate, which may help to explain drug resistance. This method offers an effective way to investigate drug mechanisms in individual cells.