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!
Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn
New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...
Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.
Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
28.09.2016 | Event News
27.09.2016 | Event News
23.09.2016 | Event News
28.09.2016 | Medical Engineering
28.09.2016 | Materials Sciences
28.09.2016 | Business and Finance