Novel Targeted Therapies a Possibility With Discovery of Enzymes Tied to Colon Cancer Tumor Growth

Investigators at the University of Massachusetts Amherst have identified a set of enzymes that are associated with the growth of colon cancer tumors, and which may be targeted to prevent or treat the disease.

In an interview with Oncology Learning Network, Guodong Zhang, PhD, Assistant Professor of Food Science, University of Massachusetts Amherst, and an investigator in the study, discussed the basis for and findings of his team’s research.

What existing data led you and your team to evaluate the role that cytochrome P450 monooxygenases play in the growth of colon cancer tumors?

A previous publication by our research team—led by Darryl C. Zeldin, MD, Division of Intramural Research, National Institute of Environmental Health Science, NIH, Research Triangle Park, North Carolina—has shown that P450 is important for primary tumor growth and metastasis (J Clin Invest. 2012;122[1]:178-191).

Please briefly describe the premise and findings of your study, highlighting any outcomes of note.

The consumption of linoleic acid (LA, 18:2ω-6), which is abundant in vegetable oil products (eg, corn, soybean, and canola oils, salad dressing, and mayonnaise), is very high in western countries.

Notably, animal experiments showed that LA increases azoxymethane-induced colorectal cancer (CRC), suggesting its potential adverse effect on CRC. However, the impact of LA on CRC in humans is inconclusive, making it difficult to make dietary recommendations for the optimal intake of LA.

Here our studies showed that LA-derived metabolites, EpOMEs, are up-regulated in colon cancer and have potent effects to promote inflammation and colon tumorigenesis. Therefore, based on our findings, overconsumption of LA could increase tissue concentrations of EpOMEs, which have potent pro-inflammatory and pro-neoplastic effects, resulting in enhanced risks of CRC.

In addition, the polymorphisms in the genes encoding CYP monoxygenases could affect LA metabolism to generate EpOMEs, which could in part explain the inconsistent results from human studies. 

Down the line, it is feasible to test whether P450 monooxygenases inhibitors could be developed for preventing or treating colon cancer.

How will this development potentially affect the treatment landscape for patients with colon cancer on a broader scale?

As we discussed above, it is feasible, from our research, that overconsumption of LA should be avoided in the individuals with or prone to colon cancer, although more research is needed before any dietary recommendation is established.

Do you and your co-investigators intend to expand upon this research?

We have got funding support from the United States Department of Agriculture to establish whether overconsumption of LA increases the risk for colon cancer via the P450 pathway.