Cell: Interpreting How Mutations Rewire Cancer Cells

In the journal of Cell, scientists have discovered how genetic cancer mutations systematically attack the networks controlling human cells, which is critical for the future development of precise& personalized cancer therapies.

Since the human genome was decoded over ten years ago, cancer genomics research has been occupying an important place in the life sciences worldwide. The identification of the individual patient and tumor mutation has achieved great success, however, the researchers were unable to link the gene mutations to their corresponding protein-the target of most pharmaceutical drugs, which seriously hampered the development of improved cancer cancer therapies.

Translating DNA mutations

Researchers from universities of Copenhagen, Yale, Zurich, Rome and Tottori have recently published two significant studies on the latest issue of the journal Cell to reveal how a causative mutation target and damage the protein signaling networks within human cells on an unprecedented scale. The research team developed a new type of software that allows researchers to study the effects of cancer mutations on protein function in individual patients.

“The identification of distinct changes within our tissues that help predict and treat cancer is a major step forward and we are confident it can aid in the development of novel therapies and screening techniques.” said Dr Rune Linding, the team leader of the project, a professor from the Biotech Research & Innovation Centre (BRIC) at the University of Copenhagen (UCPH).

“Given the tremendous amount and growth of genomic knowledge, ” explained by  Dr Pau Creixel, the first author, “a key challenge scientists face is how to interpret these data. This new software that can reveal how single DNA mutations can have dramatic molecular effects in cells by affecting critical enzymes called kinases.”

Both two studies confirmed that the cancer mutation is not just simply turn “on” or “off” the kinases, but also interfere with other proteins, thereby driving the normal cells into a more cancerous state.

Advancing personalized and tumor-specific treatment

Collaborator Dr Ben Turk, Associate Prof of Pharmacology at Yale University, indicated that “identifying mutations that effect the way that kinases regulate other proteins helps us to prioritize potential therapeutic targets, facilitating the advance of personalized medicine.”

There is a growing awareness that the genetic basis for each tumor has subtle differences. This realization has led to medical care centers investing millions of dollars to sequence individual patients and their tumors, designed to use the patient specific information to develop tailored, curative effect therapies, which is expected to help interpret the data for clinicians and researchers around the world.

“Studies like these are vital” says Dr Janine Erler, Cancer biologist and co-author, “as they enable us to better understand the behavior of tumors in both individual and groups of patients, with these twin-papers we have seriously changed gears in the fight against cancer and other complex diseases.”

Journal References:

Creixell et al. Unmasking Determinants of Specificity in the Human Kinome. Cell, September 2015 DOI: 10.1016/j.cell.2015.08.057

Creixell et al. Kinome-wide Decoding of Network Attacking Mutations Rewiring Cancer. Cell, September 2015 DOI: 10.1016/j.cell.2015.08.056