New colon cancer drugs may arise from protein discovery By Honor Whiteman

Better treatments for colon cancer may be in sight, thanks to a new study, which reveals new ways in which a single protein could stop the disease in its tracks.

Researchers found that a protein known as APC can "put the brakes" on a number of pathways that drive the development of colon cancer.

This discovery could open the door to new drugs for the condition.

Study co-author Dr. Yashi Ahmed — who works in the Norris Cotton Cancer Center at Dartmouth College's Geisel School of Medicine in Hanover, NH — and colleagues recently reported their results in the journal Developmental Cell.

Colorectal cancer — which begins in the colon or the rectum — is now the third most common cancer in the United States. It is also the third leading cause of cancer-related death.

This year, around 97,220 new cases of colon cancer are expected to be diagnosed in the U.S.

Scientists have already pinpointed APC — which is a protein endowed by the APC gene — as a possible target for the prevention of colorectal cancer; the protein regulates the growth and division of cells, stopping them from spiraling out of control and forming tumors.

On the other hand, the deactivation of APC can spur the development of colorectal cancer.

Role of APC 'broader and multifaceted'

Dr. Ahmed and colleagues explain that when it comes to the cancer-protecting role of APC, it was believed that the protein targets and destroys a single "activator" — specifically, a protein called beta-catenin — to prevent colon cancer.

By studying the APC-deficient cells of fruit flies — which harbor around 75 percent of the genes that cause human disease — the researchers uncovered other mechanisms by which APC can halt colon cancer.

"Unexpectedly," the authors say, "we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased beta-catenin levels."

Dr. Ahmed says that these findings challenge the currently accepted view of how APC prevents colon cancer, "revealing that APC's role is much broader and multifaceted."

What is more, the researchers believe that their discovery could lead to new treatments for one of the most commonly diagnosed cancers.

"Because this new role of APC involves proteins on the cell surface," explains Dr. Ahmed, "targeting colorectal cancers may become easier. For example, therapeutic antibodies, which normally cannot work inside the cell, can now be used to treat colorectal cancers that have APC mutations."

Study co-author Dr. Ethan Lee, of the Department of Cell and Developmental Biology at Vanderbilt University in Nashville, TN, adds that their study may also help researchers to understand why APC mutations appear to be a key player in specific cancers.

"Certain tissues may have a backup mechanism to put the brakes on the pathway when APC is mutated," Dr. Lee speculates.

The researchers conclude that further studies are needed to uncover the deeper details of how APC can stop colon cancer.