Molecule that provides cellular energy found key to aggressive thyroid cancer
Cancer researchers have identified a molecule they say is important to survival of anaplastic thyroid carcinoma (ATC), which is a lethal tumor with no effective therapies. The molecule also seems to play a role in a wide range of cancers.
They identified Stearoyl-CoA desaturase 1 (SCD1) as an oncogenic enzyme that when inhibited and paired with another targeted drug effectively shuts down ATC cell growth and induces cell death. Their research was presented The Journal of Clinical Endocrinology and Metabolism (2015; doi:10.1210/jc.2014-2764).
Investigators think that ATC relies on SCD1 to provide the fuel the cancer cells need to rapidly duplicate. The molecule provides this energy by promoting the cancer cell's ability to generate certain fatty acids that are important for several biological processes such as cell division, survival, drug resistance, and migration.
"We now have some hope for treatment of this cancer, which is arguably the most lethal solid tumor known to medicine," said senior author John Copland, PhD, a cancer biologist at Mayo Clinic's campus in Jacksonville, Florida. "Although ATC is rare, accounting for only 1% to 2% of thyroid cancers, it is responsible for up to 39% of all thyroid cancer-related deaths."
"Currently, there are no therapies for ATC that lead to prolonged survival, but I think combining an SCD1 inhibitor with a cocktail of other agents, all of which have dramatically different targets and approaches, may work," said co-author Robert Smallridge, MD, an endocrinologist who treats thyroid cancer.
The Mayo researchers have already developed SCD1 inhibitors and are testing the agents in different tumor models.
Cells normally take the fatty acids they need from the bloodstream, instead of making them internally, said lead author Christina von Roemeling, a graduate student and cancer researcher. She added, "But we have found this very unique switch in tumors that makes them very dependent on this method of fatty acid synthesis."
"Given the work we have done in the past several years, it is becoming really clear to us that fatty acid metabolism is quite possibly a crutch used by many cancers," von Roemeling said. "An SCD1 inhibitor might be a therapeutic target that is multipotent for several cancers, not just a one-hit wonder in a single cancer but very useful as a generic therapy."
"We have seen activity of SCD1 in a number of cancer cell lines, everything from melanoma to ovarian and breast cancer to prostate and pancreatic cancer," said Copland.
"We now have a new area of cancer therapy to explore that has not been looked at yet in anaplastic thyroid cancer," added Smallridge.