Understanding how cancer drugs work

In the focus group “Understanding how cancer drugs work”, Carl von Linde Senior Fellow Prof. Bernhard Küster and his team at the TUM School of Life Sciences seek to discover the molecular reasons underlying a phenomenon called polypharmacology. In simple terms, polypharmacology describes that a particular drug may have multiple desired or undesired effects. The former may be use to extend the application of a drug to new indications while the latter indicates toxicity. Polypharmacology is quite common but often not understood in terms of the underlying mechanism that are responsible for the one or the other effect.

Proteins are the molecular players that regulate virtually all aspects of life. The human genome encodes for about 20,000 proteins, which e. g. act as catalysts for anabolic or catabolic biochemical reactions inside cells, help to transmit signals via the network of neurons, control cell growth and division and many more. Deregulated proteins can cause severe diseases including heart or liver disorders, Alzheimer’s disease or cancer to name a few.

Because of the fundamental role of proteins in disease, most therapeutic drugs act on proteins with the goal to tone down or increase their activity. Identifying the interaction of a drug with any of the 20,000 human proteins can provide important insights into whether or not a drug works as intended or if it causes toxicity. To study protein-drug interactions systematically, the team of Bernhard Kuster brings together cellular and molecular biologists, bio- and analytical chemists as well as bioinformaticians who have established one of the world’s most powerful proteomic technology platforms. The primary focus is on cancer drugs that often show polypharmacology offering the opportunity to ‘re-purpose’ an existing drug for a new use without having to go through the very long process of discovering new drugs from scratch.