Cancers are primarily an environmental disease with 90-95% of cases attributed to environmental factors and 5-10% due to genetics. Researchers at Oxford University are interested in understanding how changes in cells' metabolism — the chemical processes through which cells get the energy they need — could also prime them to become cancerous. They have just started collaborating with a lab at Keio University in Japan to bring large-scale techniques to the study of metabolic processes going on in cancer cells, much as gene technologies have given such insight into DNA changes involved in cancers.
This is not a new finding - it is something that has been known for a long time. The biochemist and Nobel laureate Otto Warburg pointed it out in the early 1900s. He observed that most cancer cells get the energy they need predominantly through a high rate of glycolysis (the metabolic process that breaks down glucose to release energy). It helps the cancer cells deal with the low oxygen levels that tend to be present in a tumor.
But whether dysfunctional metabolism causes cancer, as Warburg believed, or is something that happens afterwards is a different question.
Cancer pathogenesis is traceable back to DNA mutations that impact cell growth and metastasis. Substances that cause DNA mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer.
DNA mutations spring up all the time in the body's cells, but most are quickly repaired. Alternatively the cell might shut down or be killed off before any damage is caused. However, the repair machinery is not perfect. If changes occur that bypass parts of the repair machinery or sabotage it, the cell can escape the body's normal controls on growth and further DNA changes can begin to accumulate as the cell switches to become cancerous.
So what has metabolism got to do with this? We get the energy we need from food of course, and we talk about our metabolism in the way our bodies make use of that food as a fuel for everything we do during the day. Our cells are the same.
Cellular metabolism is a constant process with thousands of metabolic reactions happening at the same time, all of which need to be regulated to keep our cells ticking over healthily.
It's what happens when the regulation of cellular metabolic processes goes wrong that could be of interest. And it's only a lot more recently that techniques to probe the entirety of metabolic processes in the cell have advanced. The result is something of a return to vogue for studies to understand how altered cellular metabolism and cancer are linked.
Studies of the genetic basis of cancer and dysfunctional metabolism in cancer cells are complementary, Patrick believes. "Genomic data is very important, but certain changes in cells can’t always be accounted for by genetics."
There is reason to believe that dysfunctional cell metabolism is important in cancer. Some genes with metabolic functions are associated with some cancers, and changes in the function of a metabolic enzyme have been implicated in the development of gliomas (a form of brain tumor).
These results have led to the idea that some metabolic compounds, or metabolites, when they accumulate in cells, can cause changes to metabolic processes and set cells off on a path towards cancer.
Patrick Pollard says: "Metabolic changes are observed in most cancers, so there could be wider implications. Lots of findings about pathways that are important in cancer come from studying rare cancers."
Patrick and colleagues write in their latest article that the shift in focus of cancer research to include cancer cell metabolism "has highlighted how woefully ignorant we are about the complexities and interrelationships of cellular metabolic pathways".
For further information see Cancer Fuel.
Cancer Attack Points image via Wikipedia.