This is a three-dimensional model of a tumor showing cell types in varying colors. Credit: Bartek Waclaw and Martin Nowak
The new model explains why cancer cells have a surprising number of genetic mutations in common, how driver mutations spread through the whole tumor and how drug resistance evolves. “Previously, we and others have mostly used non-spatial models to study cancer evolution,” Nowak said. “But those models do not describe the spatial characteristics of solid tumors. Now, for the first time, we have a computational model that can do that.”
A key insight of the new model, Nowak said, is the ability for cells to migrate locally. “Cellular mobility makes cancers grow fast, and it makes cancers homogenous in the sense that cancer cells share a common set of mutations. It is responsible for the rapid evolution of drug resistance,” Nowak said. “I further believe that the ability to form metastases, which is what actually kills patients, is a consequence of selection for local migration.”
In a spatial model cells divide only if they have the space to do so. This results in slow growth unless cells can migrate locally. As they divide, all cells — both healthy and cancerous — accumulate mutations, Nowak said, and most are so called “passenger” mutations that have little effect on the cell.
In cancer cells, however, ~5% are what scientists call “driver” mutations – changes that allow cells to divide faster or live longer. In addition to rapid tumor growth, those mutations carry some previous passenger mutations forward, and as a result cancer cells often have a surprising number of mutations in common. “This migration ability helps to explain how driver mutations are able to dominate a tumor, and also why targeted therapies fail within a few months as resistance evolves,” Nowak said. “So what we have is a computer model for solid tumors, and it’s this local migration that is of crucial importance.”
“…it suggests possible ways of improving cancer therapy. One of them could be targeting cellular motility (that is local migration) and not just growth as standard therapies do.” http://www.eurekalert.org/pub_releases/2015-08/hu-cc082515.php
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