Scientists from the Francis Crick Institute have uncovered the timing of significant genetic errors that fuel the proliferation of tumor growth in a variety of cell types. The current findings have begun to expose patterns that are common among many cancers and provide evidence that the growth of a tumor may rely on gene mutations that are present in only a small fraction of the cells within that tumor.

The findings from this study were published recently in Science Translational Medicine through an article entitled “Clonal status of actionable driver events and the timing of mutational processes in cancer evolution.”

The researchers sifted through genomic data from over 2,500 tumors across nine prevalent cancer types that were deposited in The Cancer Genome Atlas. The research team investigated a wide range of mutations in an attempt to expose the processes that trigger a cancerous phenotype.    

“Data from large-scale sequencing studies offer a snapshot of all the cells in a tumour at a particular moment in time,” said Charles Swanton, M.D., Ph.D., senior group leader at Cancer Research UK and senior author on the current study. “We have used a phenomenal public resource provided by the Cancer Genome Atlas in the USA to drill down further to work out how cancers change over time and to attempt to identify genetic events that in turn drive a tumour’s growth and ability to spread.”

Dr. Swanton and his colleagues analyzed the relative proportions of individual genetic errors within the data for each tumor sample. Moreover, they compared how common each genetic fault was across the different tumor types in order to compile a picture of the timing of events for tumor development.

Interestingly, the Crick Institute team found that the molecular chronology for various mutations, as well as the factors that drive them, often followed similar patterns across different tumor types.

For instance, Dr. Swanton and his team found in the latter part of tumor development for many cancer types, the cells turn on a protein called APOBEC, an RNA editing enzyme that allows the cancer cells to maintain a much higher mutation rate than normal cells. This leads to a scenario of amplified genetic diversity within the tumors that increases the changes of further mutations and drug-resistance.    

“At the moment it’s still difficult to treat cancers that have spread throughout the body, but this research provides hope that we might one day be able to predict cancer’s next evolutionary move and potentially find ways to block it,” stated Kat Arney, Ph.D., science information manager at Cancer Research UK, which funded the current study.

Understanding the genetic mutations that drive the growth and spread of disease at different time points could aid in the development of new drug therapies aimed at genetic changes present across all tumor cells. Furthermore, this could reveal ways of forcing tumors down an evolutionary dead end that makes it much less likely resistant cancer cells will be left behind to proliferate after treatment.

“It’s only the tip of the iceberg but I’m optimistic that we’ll one day be able to use evolutionary theory to outsmart many cancers, using carefully orchestrated combinations of drugs, and therapies that harness the body’s immune system, at key time points,” concluded Dr. Swanton.