Researchers Probe Proteins Instead of Mutations to Understand Cancer
Scientists from the Technical University of Munich (TUM) have decoded the proteome of 59 tumor cell lines and say that they have found new ways to explain why cancer drugs do not have the same effect on all patients suffering from the disease. The researchers based their work on the premise that it is proteins, and not mutations in DNA per se, that are ultimately responsible for changing somatic cells into cancerous ones.
The team identified over 10,000 different proteins in cancer cells. “Nearly all anti-tumor drugs are targeted against cellular proteins,” says Bernhard Küster, Ph.D., TUM chair of proteomics and bioanalytics. “Identifying the protein portfolio of tumor cells increases our chances of finding new targets for drugs.”
The researchers used NCI-60 tumor cell lines which came from the U.S. National Cancer Institute. The NCI-60 cell lines represent the most common tumor diseases in nine tissues (such as brain, breast, bowel, skin, and blood tissue). More than 5,000 of the 10,000 proteins identified are present in varying abundances in tumor cell lines of all types of tissue. “We can assume that this is the core proteome of cancer,” notes Dr. Küster. However, the researchers also found some clearly distinguishable protein profiles between the tumor cells of different tissues.
Three-hundred-seventy-five of the 10,000 proteins belong to the kinase group. “The kinases play a part in the continuous reproduction process of tumor cells,” adds Dr. Küster. “The wide variety of kinases shows how different these mechanisms are in human cancers. This is an important discovery for personalized medicine.”
The TUM group also showed that the protein pattern of the cells determines the effectiveness of cancer drugs. “We investigated how the cell lines react to 108 different cancer drugs and found that there are indeed proteins that indicate whether a cell will respond to certain therapeutic agents, or whether it will be resistant to the drug,” explains Hannes Hahne, Ph.D. a TUM expert in mass spectrometry techniques.