Thyroid Cancer Outfoxed

Thyroid cancer tumors grow with FOXO3

(RxWiki News) A molecule called FOXO3a was thought to be a keen cancer fighter. Instead, when it comes to thyroid cancer, it's actually a fox in the hen house.

FOXO3a does not suppress cancer. Instead, it supports the growth of cancer - it's a lethal cancer promoter.

A study at Mayo Clinic revealed how the molecule has outfoxed cancer researchers.

"Ask your doctor about new cancer treatments."

When FOXO3a was silenced in a model of human anaplastic thyroid cancer, scientists found that thyroid cancer cell growth slowed instead of speeding up. Scientists thought that without the protection of FOXO3a, cancer growth would explode.

"This result is exactly the opposite of what we expected," senior author John A. Copland, PhD, a Mayo cancer biologist, said. "We were more than surprised. We were concerned."

FOXO3a has been known to suppress tumor growth because it deals with the stress cells undergo, including cancer processes.

In the study, researchers used a drug to block Akt, a molecule that keeps cancer cells alive. Scientists thought that this would increase FOXO3a, which would then turn off the growth of anaplastic thyroid cancer, a rare but deadly cancer.

"We discovered a biological switch that turns FOXO3a from a good guy into a bad actor, but we don't know what that is yet, or in which cancers that might happen," said lead researcher Laura Marlow, a Mayo biologist.

Dr. Copland wants to spread the word on this and warn other researchers, including those testing Akt inhibitors (blockers).

"Cancer researchers, including those testing Akt inhibitors, should know that FOXO3a has pro-cancer activity as well as anti-cancer properties," Dr. Copland says. "Concern should be raised that an Akt inhibitor will enhance retention of FOXO3a in the nucleus, causing FOXO3a to remain active."

The study also had a bright side. A gene - cyclin A1 - was found to be involved in cancer cell growth and may become a druggable target.

This research was published in the June issue of Journal of Cell Science.

The study was funded the National Institutes of Health/National Cancer Institute, Mayo Clinic Research Committee; Florida Department of Health Bankhead-Coley Cancer Research Program; a gift from Alfred D. and Audrey M. Petersen; a grant for rare cancers from Dr. Ellis and Dona Brunton, and TGEN Institutional Research Funds.

Potential conflicts of interest were not publicly available.

Review Date: 
July 13, 2012