U lab furthers research on colon cancer treatment

By By Natalie Hale

By Natalie Hale

Researchers at the Huntsman Cancer Institute have discovered a possible way to treat patients who have colon cancer.

David A. Jones, associate professor of oncological sciences, is leading the study, which is being conducted at the cancer institute and was published in the Journal of Biological Chemistry this month.

Jones’ lab is interested in finding drugs that target the genetic defect that causes colon cancer because, as oncology researchers have discovered, there is no blanket treatment that cures all cancers.

“Eighty-five percent of colon cancers are a result of a mutation in one certain gene,” Jones said. “This mutation is found in the adenomatous polyposis gene, also known as APC.”

What Jones’ lab wanted to know is what the APC gene does when it is not mutated and what it does when it is. This gene initiates the earliest stages of the development of cells found in the intestines. When it is mutated, the cell never stops growing because it lacks the mechanism that tells the cell to turn off and die. This results in the growth of polyps in the colon, which cause cancer.

The lab’s findings suggest a more precise cause of polyp growth found within the APC gene. It is called the C-terminal Binding Protein (CtBP).

Researchers found that if they were able to genetically disable the CtBP protein, they could rescue zebra fish suffering from the APC mutation-resulting in normal intestinal growth.

In a normal cell, the APC gene controls the amount of CtPB in it by marking the cell for destruction when a certain amount of the CtPB protein is present.

In cancerous cells that have a mutated APC, the CtBP protein accumulates and the cell is never destroyed.

A known function of CtBP is the turning-off process, by which it converts vitamin A into retinoic acid in the cell. This retinoic acid is essential for creating cell differentiation, which is the specialization of cells and determines how long they survive.

The study found in both zebra fish and human tissue with APC mutations that there was a higher amount of the CtBP protein present and there was an inability to produce retinoic acid.

The researchers’ discovered that within the mutated cells where CtBP had been genetically disabled, retinoic acid production was restored.

Now, Jones’ lab is looking for compounds that will block the actions of CtBP, restoring retinoic acid production in the cells.

“We are doubly excited now because we have found that, by genetically disabling CtBP, it does not cause any major side effects,” Jones said. “Side effects limit how much of the drug can be used in treating patients. There is minimal toxicity in knocking out CtBP.”

“Thinking in terms of how research can be used to help patients is what we are trying to do,” said Reid Phelps, a researcher in Jones’ lab and a fourth-year medical Ph.D. candidate in oncological sciences. “Ideally, the work we do will lead to more specific drugs that can be used to treat colon cancer, which will have few side effects.”

Kim Peterson

David A. Jones holds a petri dish containing fish embryos injected with C-terminal Binding Protein (CtBP) inhibitors, which may help in fighting colon cancer, Monday in the Huntsman Cancer Institute.

Kim Peterson

Sophomore Chad Zavali, pre-med student studying biology, injects fish embryos with CtBP inhibitor Monday in the Huntsman Cancer Institute.