Researchers at the RIKEN Advanced Science Institute have demonstrated that a technique for tagging and profiling proteins can be used to accurately classify anti-cancer drugs based on the molecules they target. The technique, developed in collaboration with a researcher at the University of Tsukuba, promises to accelerate the process of proteomic profiling and contribute to more effective drug discovery.
While essential for effective treatment, our understanding of the complex relationship between drugs and their molecular targets is far from complete. Drug efficacy is thus low, and drugs are often accompanied by dangerous side effects. Targeted cancer therapies, which act by interfering with specific molecules contributing to tumor growth, can bring therapeutic benefits to certain patients, yet are not free of these problems. Solving them depends on connecting drugs to their molecular targets, a task complicated by the huge variety of proteins and complexity of drug-target networks.
In recent years, the field of proteomics has produced powerful techniques that simplify this task by accurately identifying proteins and their interactions. The research team used one of these techniques, two-dimensional difference gel electrophoresis (2D-DIGE), to analyze and compare changes of protein expression levels in HeLa cancer cells treated with 19 well-known anti-cancer agents. The method successfully classified compounds of different structures but sharing molecular target(s), while revealing that compounds previously reported to inhibit the same process in fact were clustered into different groups, highlighting differences in underlying interaction mechanisms.
Described in the journal Chemistry and Biology, the findings broaden the scope of proteomic profiling by enabling researchers to characterize specific compounds in terms of how they interact with biomolecules. While refining the drug discovery process, this advance also contributes to minimizing side-effects, potentially supporting the future development of safer and more effective anticancer drugs.
For more information, please contact:Dr. Hiroyuki Osada
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