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!
Scientists use nanoparticle-delivered gene therapy to inhibit blinding eye disease in rodents
08.07.2020 | Johns Hopkins Medicine
Deconstructing glioblastoma complexity reveals its pattern of development
08.07.2020 | McGill University
Biochemists at Martin Luther University Halle-Wittenberg (MLU) have used a standard electron cryo-microscope to achieve surprisingly good images that are on par with those taken by far more sophisticated equipment. They have succeeded in determining the structure of ferritin almost at the atomic level. Their results were published in the journal "PLOS ONE".
Electron cryo-microscopy has become increasingly important in recent years, especially in shedding light on protein structures. The developers of the new...
New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices
Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...
Kiel physics team observed extremely fast electronic changes in real time in a special material class
In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...
Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.
Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....
Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.
Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...
07.07.2020 | Event News
02.07.2020 | Event News
19.05.2020 | Event News
13.07.2020 | Physics and Astronomy
13.07.2020 | Life Sciences
13.07.2020 | Life Sciences