A new drug target for colorectal (large bowel) cancer has been discovered

The 10 hallmarks of cancerinclude changes in energy production. Cancer cells use metabolites (carbohydrates, fats, amino acids and their numerous byproducts) to multiply and spread to other tissues, or metastasize. Recent research suggests that discovering such cancer-related metabolites may aid early diagnosis and treatment. A study published in November 2016 in Nature Scientific Reports discovered a metabolite directly affecting colorectal cancer spread to other tissues and organs.

Metabolites are small molecules produced by chemical and biological processes in the body. Because their quantities depend on moment-to-moment cellular changes, they offer more effective results than genetic biomarkers. Among cancer-associated metabolites supporting cell growth and spread, called oncometabolites, one is D-2-hydroxyglutarate (D-2HG). Blood cancer and brain tumor cells have higher D-2-hydroxyglutarate (D-2HG) levels than normal cells. This research compared D-2-hydroxyglutarate (D-2HG) levels in normal and colorectal cancer cells to investigate its role in cancer formation.

According to the research results:

• D-2-Hydroxyglutarate levels were much higher in colorectal cancer cells than normal cells.
• When D-2-Hydroxyglutarate was delivered to cancer cells, they became more aggressive and spread rapidly.

We know that for cancer cells to spread, they must undergo epithelial–mesenchymal transition . D-2-Hydroxyglutarate was reported to increase activity of the cancer-promoting ZEB1 gene and enable epithelial–mesenchymal transition. Samples from 28 colorectal cancer patients were also examined. Patients with high D-2-Hydroxyglutarate levels showed more extensive spread to tissues and organs.

What does this study mean clinically?

• An important oncometabolite promoting colorectal cancer spread has been discovered.
• This study identified an effective drug target against metastasis. Developing drugs targeting D-2-Hydroxyglutarate may prevent colorectal cancer spread.
• In recent years, we have seen the impact on cancer of research in the new field of metabolomics . This is another important study contributed by metabolomics.