Studying Protein Networks in Bowel Cancer

PROTEOMIC study of bowel cancer cells identifies common protein mutations and allows the prediction of treatment response. For the first time, scientists have studied the role of proteins in bowel cancer pathogenesis with the hope of increasing our understanding of the underlying pathway of this common cancer and moving towards personalised medicine.

Traditional studies of cancer biology involve genome and transcriptome investigation; however, scientists from the Wellcome Trust Sanger Institute, Hixton, UK have recently completed a detailed study of the proteome in bowel cancer. Lead author, Dr Jyoti Choudhary, Wellcome Trust Sanger Institute and The Institute of Cancer Research, London, UK explained the basis of the study: “It is important to include the proteome in cancer research because proteins are the building blocks of life, and networks of proteins working together are known to drive fundamental processes in cancer.” She added: “Just studying the genome and transcriptome in the past has proven to be a blindspot in cancer research, but now including the proteome, we have the full picture.”

The team constructed coordinated networks of 9,000 proteins for 50 bowel cancer cell lines and carried out knock-out experiments of key proteins using CRISPR-Cas9. The results of the protein analysis showed that by silencing one gene, the protein levels in the rest of the network were also decreased, described by the authors as “a ripple effect”. In addition, by investigating 265 existing anti-cancer therapies on the bowel cancer cell lines, the researchers used their proteome study to effectively predict drug responses, a result which has not been successfully achieved in previous studies of the genome and transcriptome.

The authors concluded that these results confirm the value of using protein analysis to predict bowel cancer treatments, since this common cancer is composed of five different subtypes, all of which may require different drug therapies. Commenting on these promising results for bowel cancer patients, senior author Dr Ultan McDermott, Wellcome Trust Sanger Institute, said: “In the future, we may need to test the patient’s genome, transcriptome, and proteome to fully predict their response to cancer drugs and stratify patients for clinical trials more effectively. We are moving away from one size fits all towards personalised medicine.”

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