(Press-News.org) Contact information: Dan Ferber
dan.ferber@wyss.harvard.edu
617-432-1547
Wyss Institute for Biologically Inspired Engineering at Harvard
Novel noninvasive therapy prevents breast cancer formation in mice
Injectable therapy could help people avoid mastectomy
BOSTON – A novel breast-cancer therapy that partially reverses the cancerous state in cultured breast tumor cells and prevents cancer development in mice, could one day provide a new way to treat early stages of the disease without resorting to surgery, chemotherapy or radiation, a multi-institutional team led by researchers from the Wyss Institute of Biologically Inspired Engineering at Harvard University reported January 1 in Science Translational Medicine.
The therapy emerged from a sophisticated effort to reverse-engineer gene networks to identify genes that drive cancer. The same strategy could lead to many new therapies that disable cancer-causing genes no current drugs can stop, and it also can be used to find therapies for other diseases.
"The findings open up the possibility of someday treating patients who have a genetic propensity for cancer, which could change people's lives and alleviate great anxiety," said Don Ingber, M.D., Ph.D., Wyss Institute Founding Director. "The idea would be start giving it early on and sustain treatment throughout life to prevent cancer development or progression." Ingber is also the Judah Folkman Professor of Vascular Biology at Boston Children's Hospital and Harvard Medical School, and Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences.
Between breast self-exams, mammograms, MRIs, and genetic tests, more women than ever are undergoing early tests that reveal precancerous breast tissue. That early diagnosis could potentially save lives; however, few of those lesions go on to become tumors and doctors have no good way of predicting which ones will. As a result, many women currently undergo surgery, chemotherapy and radiation who might never develop the disease. What's more, some women with a high hereditary risk of breast cancer have chosen to undergo preemptive mastectomies.
A therapy that heals rather than kills cancerous tissue could potentially help all these patients, as well as men who develop the disease. But to date the only way to stop cancer cells has been to kill them. Unfortunately, the treatments that accomplish that, including surgery, chemotherapy, and radiation therapy, often damage healthy tissue, causing harsh side effects.
The Wyss Institute researchers thought they could do better by spotting new genes that drive breast cancer and developing targeted genetic therapies to block them. First they had to identify the culprit genes among the thousands that are active in a cell at any moment. Molecular biologists typically convict these culprits through guilt by association; for example, when looking for cancer-causing genes, they search for individual genes that become active as cancer develops. But because genes in cells work in complex networks, that approach has led to some false convictions, with innocent genes being fingered for crimes they did not commit.
To improve the odds of finding the real culprits, Ingber teamed up with Wyss Institute Core Faculty member Jim Collins, Ph.D., a systems biology expert who has developed a sophisticated mathematical and computational method to reverse-engineer bacterial gene networks. Collins is a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering and the William F. Warren Distinguished Professor at Boston University, where he leads the Center of Synthetic Biology.
First, Hu Li, Ph.D. a former Wyss Institute postdoctoral fellow who is now an Assistant Professor of Systems Pharmacology at the Mayo Clinic, honed the computational network to work for the first time on the more complex gene networks of mice and humans. The refined method helped the scientists spot more than 100 genes that acted suspiciously just before milk-duct cells in the breast begin to overgrow. The team narrowed their list down to six genes that turn other genes on or off, and then narrowed it further to a single gene called HoxA1 that had the strongest statistical link to cancer.
The researchers wanted to know if blocking the HoxA1 gene could reverse cancer in lab-grown cells from mouse milk ducts. Amy Brock, Ph.D., a former Wyss Institute postdoctoral fellow who is now an Assistant Professor of Biomedical Engineering at the University of Texas, Austin, grew healthy mouse or human mammary-gland cells in a nutrient-rich, tissue-friendly gel. Healthy cells ensconced in the gel formed hollow spheres of cells akin to a normal milk duct. But cancerous cells, in contrast, packed together into solid, tumor-like spheres.
Brock treated cancerous cells with a short piece of RNA called a small interfering RNA (siRNA) that blocks only the HoxA1 gene. The cells reversed their march to malignancy, stopping their runaway growth and forming hollow balls as healthy cells do. What's more, they specialized as if they were growing in healthy tissue.
The siRNA treatment also stopped breast cancer in a line of mice genetically engineered to have a gene that causes all of them to develop cancer. The Wyss team worked with Michael Goldberg, Ph.D., Assistant Professor of Microbiology and Immunobiology at Harvard Medical School and the Dana-Farber Cancer Institute, to leverage a novel method he had developed to deliver the siRNA efficiently.
They packed the siRNA into nanoparticles called lipidoids that allow for genes to be silenced for weeks inside the body. They then did something unusual: they injected these nanoparticles directly through the nipples into the milk ducts of the cancer-prone mice, using a new method that Silva Krause, Ph.D., a postdoctoral fellow on Ingber's team, had developed. This is important because the cells that line the ducts are the ones that form breast tumors in mice as well as humans.
Weeks went by as Brock and Krause watched. The treated mice remained healthy, while untreated mice developed breast cancer. "There was no aha moment," Brock said. "But after enough evidence builds up, you turn to each other and say this is really doing something here," Brock said.
"We were delighted that we could reverse-engineer mammalian gene networks to identify key disease-causing genes, and we're hopeful that our approach can help uncover new drug targets for many hard-to-treat cancers," Collins said.
Indeed, the work marks a milestone not just in breast cancer research, but in systems biology, Ingber said. "Combining computational, engineering and biological approaches has led to a new way to identify drugs that prevent cancer development and progression."
INFORMATION:
The work was funded by the Department of Defense Breast Cancer Innovator award provided to Don Ingber, the Howard Hughes Medical Institute, SysCODE (Systems-based Consortium for Organ Design & Engineering), the National Institutes of Health, a Susan G. Komen Foundation postdoctoral fellowship to Silva Krause, and the Wyss Institute. In addition to Brock, Krause, Li, Goldberg, Collins and Ingber, the authors included Marek Kowalski, a former research assistant at the Wyss Institute.
PRESS CONTACT
Wyss Institute for Biologically Inspired Engineering at Harvard University
Dan Ferber
dan.ferber@wyss.harvard.edu
+1 617-432-1547
IMAGE AVAILABLE
The Wyss Institute for Biologically Inspired Engineering at Harvard University uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard's Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, and Charité - Universitätsmedizin Berlin, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature's principles, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.
The Boston University College of Engineering offers a wide range of undergraduate, graduate and professional degrees in foundational and emerging engineering disciplines. Underlying the College's educational efforts is its commitment to creating Societal Engineers, who have an appreciation for how the engineer's unique skills can be used to improve our quality of life. Ranked among the nation's best engineering research institutions, the College's faculty attracts more than $50 million in external research support annually.
Novel noninvasive therapy prevents breast cancer formation in mice
Injectable therapy could help people avoid mastectomy
2014-01-02
ELSE PRESS RELEASES FROM THIS DATE:
Research into fruit fly cells could lead to cancer insights
2014-01-02
Research into fruit fly cells could lead to cancer insights
New research by scientists at the University of Exeter has shown that cells demonstrate remarkable flexibility and versatility when it comes to how they divide - a finding with potential links ...
Alcohol, tobacco, drug use far higher in severely mentally ill
2014-01-02
Alcohol, tobacco, drug use far higher in severely mentally ill
In the largest ever assessment of substance use among people with severe psychiatric illness, researchers at Washington University School of Medicine in St. Louis and the University of Southern ...
Tripling tobacco taxes worldwide would avoid 200 million tobacco deaths
2014-01-02
Tripling tobacco taxes worldwide would avoid 200 million tobacco deaths
Controlling tobacco marketing is also key to helping people quit smoking
TORONTO, Jan. 2, 2014—Tripling taxes on cigarettes around the world would reduce the number of smokers by one-third ...
US global share of research spending declines
2014-01-02
US global share of research spending declines
New analysis shows Asia gaining, due to increased support from both government, industry
ANN ARBOR, Mich. — The United States' global share of biomedical research spending fell from 51 percent in 2007 ...
Drivers engaged in other tasks about 10 percent of the time
2014-01-02
Drivers engaged in other tasks about 10 percent of the time
NIH, Virginia Tech study shows crash risks greatest for teens
Drivers eat, reach for the phone, text, or otherwise take their eyes off the road about 10 percent of the time ...
High blood pressure potentially more dangerous for women than men
2014-01-02
High blood pressure potentially more dangerous for women than men
WINSTON-SALEM, N.C. – Jan. 2, 2014 – Doctors may need to treat high blood pressure in women earlier and more aggressively than they do in men, according to scientists at Wake Forest ...
To grow or to defend: How plants decide
2014-01-01
To grow or to defend: How plants decide
Crop breeding for semi-dwarfed plants could also improve disease resistance
Scientists have discovered how plants use steroid hormones to choose growth over defence when their survival depends on it.
The findings ...
Insight into likelihood of retinal detachment following open globe injury
2014-01-01
Insight into likelihood of retinal detachment following open globe injury
Findings published in Jan. issue of Ophthalmology
BOSTON (Jan. 1, 2014) – Ocular trauma causing open globe injury, or a breach in the wall of the eye, remains an important ...
New molecular targets identified in some hard-to-treat melanomas provide potential treatment option
2013-12-31
New molecular targets identified in some hard-to-treat melanomas provide potential treatment option
December 30, 2013 New York, NY / Los Angeles, CA: Stand Up To Cancer (SU2C), the charitable initiative supporting ground-breaking research ...
Sleep to protect your brain
2013-12-31
Sleep to protect your brain
A new study from Uppsala University, Sweden, shows that one night of sleep deprivation increases morning blood concentrations of NSE and S-100B in healthy young men. These molecules are typically found in the brain. Thus, ...
LAST 30 PRESS RELEASES:
Pink skies
Monkeys are world’s best yodellers - new research
Key differences between visual- and memory-led Alzheimer’s discovered
% weight loss targets in obesity management – is this the wrong objective?
An app can change how you see yourself at work
NYC speed cameras take six months to change driver behavior, effects vary by neighborhood, new study reveals
New research shows that propaganda is on the rise in China
Even the richest Americans face shorter lifespans than their European counterparts, study finds
Novel genes linked to rare childhood diarrhea
New computer model reveals how Bronze Age Scandinavians could have crossed the sea
Novel point-of-care technology delivers accurate HIV results in minutes
Researchers reveal key brain differences to explain why Ritalin helps improve focus in some more than others
Study finds nearly five-fold increase in hospitalizations for common cause of stroke
Study reveals how alcohol abuse damages cognition
Medicinal cannabis is linked to long-term benefits in health-related quality of life
Microplastics detected in cat placentas and fetuses during early pregnancy
Ancient amphibians as big as alligators died in mass mortality event in Triassic Wyoming
Scientists uncover the first clear evidence of air sacs in the fossilized bones of alvarezsaurian dinosaurs: the "hollow bones" which help modern day birds to fly
Alcohol makes male flies sexy
TB patients globally often incur "catastrophic costs" of up to $11,329 USD, despite many countries offering free treatment, with predominant drivers of cost being hospitalization and loss of income
Study links teen girls’ screen time to sleep disruptions and depression
Scientists unveil starfish-inspired wearable tech for heart monitoring
Footprints reveal prehistoric Scottish lagoons were stomping grounds for giant Jurassic dinosaurs
AI effectively predicts dementia risk in American Indian/Alaska Native elders
First guideline on newborn screening for cystic fibrosis calls for changes in practice to improve outcomes
Existing international law can help secure peace and security in outer space, study shows
Pinning down the process of West Nile virus transmission
UTA-backed research tackles health challenges across ages
In pancreatic cancer, a race against time
Targeting FGFR2 may prevent or delay some KRAS-mutated pancreatic cancers
[Press-News.org] Novel noninvasive therapy prevents breast cancer formation in miceInjectable therapy could help people avoid mastectomy