Though cancer is a genetic disease, the environment and metabolism must also be considered – and could narrow down avenues for cancer treatment, according to a research review by a leading expert which appears in Metabolites.
Nearly all the theories about the causes of cancer that have emerged over the past several centuries can be sorted into three larger groups, said Professor David Wishart at the University of Alberta. The first is cancer as a genetic disease, focusing on the genome. The second is cancer as an environmental disease, focusing on the exposome, which includes everything the body is exposed to throughout life. The third is cancer as a metabolic disease, focusing on the metabolome, which is all the chemical byproducts of the process of metabolism.
Until now, there has been little research on the metabolic perspective, but it’s gaining the interest of more scientists, who are beginning to understand the metabolome’s role in cancer.
The genome, exposome and metabolome operate together in a feedback loop as cancer develops and spreads.
According to the data, heritable cancers account for only 5–10%of all cancers, Wishart said. The remaining 90–95% are initiated by factors in the exposome, which in turn trigger genetic mutations.
“That’s an important thing to consider, because it says that cancer isn’t inevitable.”
The metabolome is a crucial part of the process, as those genetically mutated cancer cells are sustained by the cancer-specific metabolome.
“Cancer is genetic, but often the mutation itself isn’t enough,” said Wishart. As cancer develops and spreads in the body, it creates its own environment and introduces certain metabolites. “It becomes a self-fuelled disease. And that’s where cancer as a metabolic disorder becomes really important.”
The multi-omics perspective considers the genome, exposome and metabolome in unison when thinking about cancer. It is showing promise for finding treatments and for overcoming the limitations of looking at only one of these factors.
Researchers focusing only on the genetic perspective, for example, are looking to address particular mutations. The problem is, Prof Wishart said, is that there are around 1000 genes that can become cancerous when mutated, at least two different mutations within these cells are usually for cancer to grow. Thus, a there are a million possible mutation pairs, so “it becomes hopeless” to narrow down the possibilities when seeking new treatments.
From the metabolic perspective, there are just four major metabolic types, said Prof Wishart. Therefore instead of searching for a treatment plan for a one in a million mutation combination, determining the patient’s cancer metabolic type can immediately guide doctors in deciding on the best treatment for their specific cancer.
“It really doesn’t make a difference where the cancer is – it’s something you’ve got to get rid of. It’s how it thrives or grows that matters,” said Prof Wishart. “It becomes a question of, ‘What’s the fuel that powers this engine?'”
However, health-care providers still need a mix of therapeutics for cancer, and he noted that a deeper understanding of the metabolome and its role in the cancer feedback loop is also critical to preventing cancer.
“If we understand the causes of cancer, then we can start highlighting the known causes, the lifestyle issues that introduce or increase our risk,” he said.
“From the prevention side, changing our metabolism through lifestyle adjustments will make a huge difference in the incidence of cancer.”
Source: University of Alberta
