Their report, published online in Gynecologic Oncology, suggests that this combination (ixabepilone and sunitinib), might offer a much needed treatment option for women with advanced ovarian cancer. When caught at late stages, ovarian cancer is often fatal because it progressively stops responding to the chemotherapy drugs used to treat it.
"Women die from ovarian cancer because their tumors become resistant to chemotherapy, so a drug that might be able to reduce that resistance — which may be what this combination of agents is doing — would be a boon to treatment of this difficult cancer," says study co-author Gerardo Colon-Otero, M.D., a hematologist-oncologist who cares for ovarian cancer patients.
The finding also highlights the importance of the role of a molecule, RhoB, that the researchers say is activated by the drug duo. The study's senior investigator, cancer biologist John Copland, Ph.D., has identified RhoB as a key modulator for drug response in other tumor types, but says its role in ovarian cancer was unknown before this study.
"Now we find that with this combination of drugs, RhoB is increased and cells die," he says.
The study was possible because Dr. Copland and his laboratory colleagues, including co-author Laura Marlow, created and characterized two new ovarian laboratory cell lines. They were derived from tumor tissue specimens taken from a patient with metastatic cancer whose tumors had stopped responding to multiple chemotherapy drugs.
Dr. Colon-Otero suggested trying the two drugs on the new cells lines. Neither drug is approved for use in ovarian cancer. Ixabepilone is a chemotherapy drug that, like other taxane drugs, targets the microtubules and stops dividing cells from forming a spindle. It has been approved for use in metastatic breast cancer. Sunitinib, approved for use in kidney cancer, belongs to a class of tyrosine kinase inhibitors that stops growth signals from reaching inside cancer cells.
Prakash Vishnu, M.D., a former fellow at Mayo Clinic in Florida who is now at the Floyd and Delores Jones Cancer Institute in Virginia Mason Medical Center, Seattle, is the first author of the article and led the study under the mentorship of Drs. Colon-Otero and Copland. He found that in both cell lines, cell kill was significantly greater with the combination than use of either drug alone. For example, in chemotherapy-resistant lines (where this potential combination therapy will most likely be used), ixabepilone alone killed up to 30 percent of cells, and the rate for suntinib was up to 10 percent. When the agents were used together, the kill rate was 70 percent.
Dr. Copland said that RhoB is a potential biomarker that may help identify patients who might benefit from such combination therapy.
The study was funded by Mayo Clinic. Additional co-authors included Joseph Santoso, M.D., of the University of Tennessee and Kevin Wu, M.D., of Mayo Clinic, as well as undergraduate students Gregory Kennedy and William Kennedy from Dr. Copland's laboratory. The researchers declare no conflicts of interest.
Kevin Punsky | EurekAlert!
When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie
WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences