In the online issue of Molecular Cancer Therapeutics, they report that two drugs, romidepsin and decitabine, work cooperatively to activate a potent tumor suppressor gene that is silenced in these cancers. Once the gene, secreted frizzled related protein one or sFRP1, went to work after the drugs were used, the laboratory tumor cells stopped growing and died.
Both drugs are approved by the Food and Drug Administration to treat blood cancer and are being tested individually in numerous solid cancers in which sFRP1 is disabled. This study was the first to test the use of both in these metastatic cancers linked to sFRP1, and the results are very encouraging, says senior investigator John Copland, Ph.D., a Mayo Clinic molecular biologist.
"We now have the basis for a clinical trial aimed at providing effective therapy for two drug-resistant cancers and perhaps many more tumor types in the future," Dr. Copland says. In addition to breast and kidney cancer, sFRP1 is disabled in colon, ovarian, lung, liver and other tumor types.
Dr. Copland and his colleagues earlier discovered that sFRP1 was silenced in certain cancers. This new work demonstrates that its expression can be restored by romidepsin, which is a histone deacetylase inhibitor, and decitabine, a methyltranferase inhibitor. Both are epigenetic drugs, modifying genes in a way that affects whether they are turned on or off.
"Individually, each drug did not induce any form of cell death but, together, they killed all of the different cell lines of kidney and triple negative breast cancer that we tested in the laboratory," says lead investigator Simon Cooper, Ph.D., a Mayo Clinic molecular biologist who specializes in renal cancer.
The two cancers affect up to 80,000 Americans each year and therapies to treat both, especially when they are advanced, have been very limited, says co-author Edith Perez, M.D., deputy director of Mayo Clinic Cancer Center.
"But now, not only do we have a very promising lead on future therapy, but if this combination treatment works as we hope it does, we will have a biomarker to be able to test which patients might benefit the most," she says. "In other words, a biopsy test could identify patients whose tumors had lost sFRP1 function."
The approach to finding this potential new treatment strategy is novel, adds oncologist Michael Menefee, M.D., who is also a study co-author.
"This type of interdisciplinary preclinical research effort is important, not only because of the value of the science, but also because the drugs are already in the clinic and that will facilitate translational efforts and hopefully confirm the preclinical findings in patients with advanced malignancies," he said.
Other study co-authors include Christina A. von Roemeling; Kylie H. Jang; Laura A. Marlow, M.S.; Stefan K. Grebe, M.D.; Han W. Tun, M.D.; and Gerardo Colon-Otero, M.D.
The study was funded in part by grants from the National Institutes of Health, the David & Lois Stulberg Endowed Fund for Kidney Cancer Research, the Breast Cancer Research Foundation, James C. and Sarah K. Kennedy Mayo Clinic Research Career Development Award for Clinicians, The Brenda E. and Roger S. Luca Family Endowment at The Tallahassee Memorial HealthCare Foundation, RITA Foundation (Research Is The Answer), Scheidel Foundation, and a grant for rare cancers from Dr. Ellis and Dona Brunton.
About Mayo Clinic Cancer Center
As 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.
About Mayo Clinic
Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit MayoClinic.com or MayoClinic.org/news.
Paul Scotti | EurekAlert!
NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)
High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses