Big Step Toward Developing Targeted Cancer Treatments

Scientists still don't really understand why some people develop cancer and others don't. But, research findings at the University of Alberta confirm that genetics can play a role in the development of cancer, just like environmental and metabolic factors. Although cancer is a genetic disease, the genetic component is only part of the mystery — and researchers should also consider environmental and metabolic factors, according to a research review by a leading expert at the University of Alberta.

The Three Causes of Cancer

David Wishard, a professor of Biological Sciences and Computer Science, said that all theories about the causes of cancer that have emerged over the past several centuries can be grouped into three major groups.

• The first cancer is a genetic disorder called “genome”, focusing on a set of genes or genetic mechanisms by which you are born.
• Second, cancer is an environmental disease called “exposome” in which your body focuses on all-encompassing exposure throughout your life.
• The third cancer is a metabolic disease that focuses on metabolism called “metabolome”, all chemical by-products of the metabolic process.

The metabolome, which refers to all of the small-molecule metabolites found in a cell, is an unheralded player in cancer research.

The metabolic perspective does not have much research yet, but it is of interest to more and more scientists who are beginning to understand the metabolome’s role in cancer.

Genome, exposome, and metabolome work together in the feedback cycle as cancer develops and spreads.

The Cancer-Specific Metabolome

Wishart had informed that heritable cancers account for just 5% to 10% of all cancers and the remaining cancers are initiated by factors like the exposome, which in turn trigger genetic mutations.

“That’s an important thing to consider, because it says that cancer isn’t inevitable.” Because genetically modified cancer cells are retained by cancer-specific metabolome, metabolome are important to the process.

Wishart said, “Cancer is genetic, but often the mutation itself isn’t enough.” 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, in which the genome, exposome, and metabolome are all considered in unison when thinking about cancer, is showing promise for finding treatments and for overcoming the limitations of looking at only one of these factors.

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For example, as Wishart explained, researchers who focus only on the genetic perspective are looking to address particular mutations. The problem is, there are around 1,000 genes that can become cancerous when mutated, and it typically takes at least two different mutations within these cells for cancer to grow. That means there are a million potential mutation pairs, and “it becomes hopeless” to narrow down the possibilities when seeking new treatments.

Wishart has explained that when considering cancer from the metabolic perspective, there are just four major metabolic types. Rather than trying to find a treatment plan for one specific mutation combination amongst a million, determining the patient’s cancer metabolic type can immediately guide doctors in deciding on the best treatment for their specific cancer.

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Wishart told, “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,” on a discussion about cancer. “It becomes a question of, ‘What’s the fuel that powers this engine?’”

He also cautioned that health-care providers still need a mix of therapeutics for cancer, and noted that a deeper understanding of the metabolome and its role in the cancer feedback loop is also critical to preventing cancer.

He had said, “If we understand the causes of cancer, then we can start highlighting the known causes, the lifestyle issues that introduce or increase our risk.”

“From the prevention side, changing our metabolism through lifestyle adjustments will make a huge difference in the incidence of cancer.”

Understanding this discovery is a big step toward developing targeted cancer treatments that target the metabolism of cancer cells, without affecting the metabolism of healthy cells.

This research was funded by the Genome Canada, the Canadian Institutes of Health Research, and the Canada Foundation for Innovation.

Source-Medindia