The inexpensive anti-malarial drug hydroxychloroquine (HCQ) reverses resistance to tamoxifen, a widely used breast cancer drug, in mice.
In the June 15 issue of Clinical Cancer Research, investigators from Georgetown Lombardi Comprehensive Cancer Center say adding HCQ to tamoxifen could provide a new treatment option for some women with advanced, postmenopausal estrogen receptor-positive (ER+) breast cancer. The ER+ subtype accounts for an estimated 70 percent of all breast cancers. While many of these women are treated with tamoxifen, which blocks estrogen from fueling the tumor, 50 percent of these cancers will either not respond or will become resistant to tamoxifen over time.
"Tamoxifen resistance when treating breast cancer is a big issue in the clinic, and we believe our findings provide a very promising fix to the problem," says the study's senior investigator, Robert Clarke, PhD, DSc, dean for research at Georgetown University Medical center, and co-director of the breast cancer program at Georgetown Lombardi.
Clarke adds that both drugs are inexpensive, on the market and have a well-defined safety profile.
HCQ was developed to treat malaria, but has since been repurposed as therapy for rheumatoid arthritis and lupus. The study is the first to test HCQ's ability to restore breast cancer cell sensitivity to tamoxifen or to a different anti-estrogen drug known as faslodex.
The research team, led by first author Katherine Cook, PhD, a postdoctoral research fellow in the tumor biology department at Georgetown Lombardi, purposely set out to test HCQ in mice with either tamoxifen or faslodex-resistant human breast cancer cells.
Previous research led by Clarke and Cook found that tamoxifen resistance occurs because a pro-survival pathway is switched on in breast cancer cells. HCQ functions by turning off that very same molecular pathway, Cook says.
The researchers found that the combination of tamoxifen and HCQ is more effective than faslodex and HCQ due to activities within the tumor's microenvironment. "Faslodex and tamoxifen, while both effective as antiestrogen therapies, have different effects on the immune system thus making the combination of faslodex and HCQ less effective," says Cook.
"Many people have been trying combinations of drugs to restore the ability of tamoxifen to fight breast cancer. We believe this pairing is very worthy of additional research, as well as clinical study," she says.
The study is supported by a Department of Defense Breast Cancer Research Program Postdoctoral Fellowship (BC112023) and awards from the US Department of Health and Human Services (R01-CA131465 and U54-CA149147).
The authors have no conflicts of interest.
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.
Karen Teber | Eurek Alert!
A 'half-hearted' solution to one-sided heart failure
24.11.2017 | Boston Children's Hospital
New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University
High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons
The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
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...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
24.11.2017 | Physics and Astronomy
24.11.2017 | Health and Medicine
24.11.2017 | Earth Sciences