The two drugs together resulted in greater anti-cancer activity in ATC than either drug alone, says lead researcher Keith Bible, M.D., Ph.D., a Mayo Clinic oncologist.
Anaplastic thyroid cancer is a rare but devastating form of thyroid cancer that typically strikes men and women in their 60s and 70s. It is very aggressive, with a median survival of only about 5 months from time of diagnosis. Only 20 percent of patients survive a year beyond diagnosis, and it has historically been found to be resistant to most therapies.
Pazopanib, a kinase-inhibitor that interferes with the growth of cancer cells, is already approved by the Food and Drug Administration (FDA) to treat renal cancer tumors. Paclitaxel is an FDA-approved chemotherapy drug that disrupts the machinery involved in cell division.
Researchers studied anaplastic thyroid cancer cells and tumors in cell culture and in animal models. Human ATC cells were readily killed, and ATC tumors implanted into mice were 50 percent smaller when treated with the combination in comparison to the response to treatment with either drug alone. Pilot therapy of one patient with metastatic anaplastic thyroid cancer using the combination also resulted in marked tumor shrinkage lasting over six months. "This was a highly unexpected finding for this type of aggressive tumor, which often can double in size in a matter of days," Dr. Bible says.
In previous studies, pazopanib alone was found not effective in the treatment of anaplastic thyroid cancer. Paclitaxel was added to address the aggressiveness of anaplastic thyroid cancer tumors and bolster anti-cancer effects. The team investigated how the two drugs might complement each other.
Monitoring cancer cells multiply in time-lapse video under a microscope, researchers noted that the drug combination resulted in abnormal cell division and an increase in ATC cell death. Although pazopanib had not been known to specifically affect cell division, researchers speculated that the drug might have another unrecognized molecular target within cancer cells.
"We ended up learning that pazopanib also happens to inhibit a protein involved in cell division known as aurora A; this property seems to be involved in producing enhanced effects when pazopanib is combined with paclitaxel," Dr. Bible says. "This finding suggests that the combination may also be useful in treating other cancers, such as breast cancer, in which aurora A is sometimes found to be present in elevated amounts, as it is in ATC," Dr. Bible says.
The results also prompted an ongoing randomized multicenter clinical trial, led by Mayo Clinic and Memorial Sloan-Kettering Cancer Center and administered through the Radiation Therapy Oncology Group, testing the two-drug combination when added to radiation therapy in the initial treatment of patients with anaplastic thyroid cancer.
"This important next step is designed to determine whether the combination of drugs will improve ATC patient survival compared to paclitaxel alone," Dr. Bible says.
The research was funded by National Institutes of Health grants CA125750 and CA13666 and the State of Florida Department of Health Bankhead-Coley Cancer Program. Co-authors include Crescent Isham, Ayoko Bossou, Vivian Negron, Wilma Lingle, Ph.D., Vera Suman, Ph.D. of Mayo Clinic in Rochester, Robert Smallridge, M.D., John Copland, Ph.D., and Laura Marlow of Mayo Clinic in Jacksonville, Fla.; Kelly Fisher and Rakesh Kumar, Ph.D., of GlaxoSmithKline; and Eric Sherman, M.D., of Memorial Sloan-Kettering Cancer Center.
About Mayo Clinic Cancer CenterAs a leading institution funded by the National Cancer Institute, Mayo Clinic Cancer Center conducts basic, clinical and population science research, translating discoveries into improved methods for prevention, diagnosis, prognosis and therapy. For information on cancer clinical trials, call 507-538-7623.
Journalists can become a member of the Mayo Clinic News Network for the latest health, science and research news and access to video, audio, text and graphic elements that can be downloaded or embedded.
Joe Dangor | EurekAlert!
Real-time imaging of lung lesions during surgery helps localize tumors and improve precision
30.07.2015 | American Association for Thoracic Surgery
Experimental MERS vaccine shows promise in animal studies
29.07.2015 | NIH/National Institute of Allergy and Infectious Diseases
Glacier decline in the first decade of the 21st century has reached a historical record, since the onset of direct observations. Glacier melt is a global phenomenon and will continue even without further climate change. This is shown in the latest study by the World Glacier Monitoring Service under the lead of the University of Zurich, Switzerland.
The World Glacier Monitoring Service, domiciled at the University of Zurich, has compiled worldwide data on glacier changes for more than 120 years. Together...
Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.
What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...
Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.
The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...
Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.
Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight
A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...
23.07.2015 | Event News
10.07.2015 | Event News
25.06.2015 | Event News
03.08.2015 | Materials Sciences
03.08.2015 | Life Sciences
03.08.2015 | Life Sciences