Study uncovers new enzyme map which could lead to better cancer treatments

A team of biologists say they are hopeful their research, which mapped out more than 300 protein kinases and its targets, could help pave the way for new cancer curing drugs. 

Scientists have focused on protein kinases research because of its role in how diseases, particularly cancer, develop, but the unknowns about specific cellular pathways have hampered progress in finding potential drug targets. 

“We have a lot of sequencing data for cancer genomes, but what we’re missing is the large-scale study of signaling pathway and protein kinase activation states in cancer. If we had that information, we would have a much better idea of how to drug particular tumors,” Michael Yaffe, a Massachusetts Institute of Technology professor and director of the MIT Center for Precision Cancer Medicine, said in a press release.

The research lead by Yaffe, Lewis Canley of Harvard Medical School, and Benjamin Turk of Yale's School of Medicine, pinpointed an atlas of more than 300 protein kinases found in human cells, which provided insight on their target proteins and regulatory functions, according to the press release. The team's findings were published in the journal Nature which highlighted the research which has opened doors for a deeper knowledge of how these proteins are managed in diseases. 

The start of the collaboration among the three scientists dates 25 years ago. Pharmacology instructor Jared Johnson and graduate student Tomer Yaron, both of Weill Cornell Medical College, were the paper's lead authors. The study focused on both serine and threonine kinases, which make up about 85% of all protein kinases in the human body. They examined the kinases structural motifs and used a library of peptides that Cantley and Turk created, and then studied how the peptides interacted with the 303 known serine and threonine kinases, the press release stated.

According to the release, their findings shockingly revealed that numerous kinases with distinct amino acid sequences had evolved to bind and phosphorylate the same motifs on substrates. The researchers also found that about half of the kinases targeted one of three major classes of motifs, while the remaining half were specific to around a dozen smaller classes. The newly created map established an important tool for researchers, which will allow them to distinguish signaling pathways unique to normal and cancerous cells, as well as treated and untreated cancer cells. Through the map it's possible previously unknown signaling pathways that cause cancer and aid in personalized treatment approaches will be found. 

The research was made possible through the support of various organizations including the Leukemia and Lymphoma Society, the National Institutes of Health, Cancer Research UK, the Brain Tumour Charity, the Charles and Marjorie Holloway Foundation, the MIT Center for Precision Cancer Medicine, and the Koch Institute Support (core) grant from the National Cancer Institute.