Breaking News
February 20, 2019 - Over Half of Hip Replacements Expected to Last 25 Years
February 20, 2019 - Microscopic eye movements affect how we see contrast
February 20, 2019 - Computer vs. patient: Fighting for residents’ attention | News Center
February 20, 2019 - New “Smart Drug” Shows Promise for Metastatic Triple-Negative Breast Cancer
February 20, 2019 - Researchers develop large-scale window material for high-efficiency PM2.5 capture
February 20, 2019 - Widespread confusion among consumers on food date labels lead to unnecessary discards
February 20, 2019 - Researchers unlock plant’s secret of producing specialized metabolites
February 20, 2019 - Newly released national framework identifies obstacles to improving EMS systems
February 20, 2019 - Exercise can shift human body clock depending on time when people work out
February 20, 2019 - Female adolescent blood donors more likely to have iron deficiency and related anemia
February 20, 2019 - Rubicon level linked to inhibition of autophagic process
February 20, 2019 - Researchers find potential therapeutic strategy to treat Alzheimer’s
February 20, 2019 - New forms of older anti-cancer agent appear to enhance immune response to fight melanoma
February 20, 2019 - Health Tip: Eat Less Saturated Fat
February 20, 2019 - Sleeping in contact lenses puts you at risk of dangerous infection
February 20, 2019 - “We should study that!”: How a nurse-scientist found her passion
February 20, 2019 - Cervical microbiome may influence HPV infection more than previously thought
February 20, 2019 - Sausage mislabeling in Canada is down, new study finds
February 20, 2019 - Study shows blood pressure benefits of morning exercise for older overweight/obese adults
February 20, 2019 - New screening method could catch organ rejection much earlier without a biopsy needle
February 20, 2019 - Study may have important implications for refining parenting during child’s adolescence
February 20, 2019 - Study sheds new light on how antibiotic resistance genes are transferred between bacteria
February 20, 2019 - Chronic Wasting Disease may soon spread to humans, warns CDC
February 20, 2019 - Scientists identify new genetic causes linked to abnormal pregnancies and miscarriages
February 20, 2019 - Using LyoSpeed technology to avoid residual solvent when drying HPLC fractions
February 20, 2019 - Scientists join forces to identify a new approach to fight African sleeping sickness
February 20, 2019 - New screening tool more likely to identify sexual and labor exploitation of youth
February 20, 2019 - Newly licensed nurses work for long hours, also have a second paid job
February 20, 2019 - Physicists identify simple mechanism used by deadly bacteria to fend off antibiotics
February 20, 2019 - FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib
February 20, 2019 - Exposure to chemicals before and after birth is associated with a decrease in lung function
February 20, 2019 - Neuroscientists reveal that simple brain region can guide complex feats of mental activity
February 20, 2019 - Study finds new link between food allergies and multiple sclerosis
February 20, 2019 - First gene therapy operation for macular degeneration is a success
February 20, 2019 - Physicians graduated outside the U.S. offer better care for Medicare patients with complex needs
February 20, 2019 - Study shows therapeutic potential of VEGF-A mRNA for regenerative angiogenesis in humans
February 20, 2019 - FDA Approves Keytruda (pembrolizumab) for the Adjuvant Treatment of Patients with Melanoma with Involvement of Lymph Node(s) Following Complete Resection
February 20, 2019 - Study identifies brain cells that modulate behavioral response to threats
February 20, 2019 - Researchers take closer look at how viruses bind cells and cause infection
February 20, 2019 - Newly developed gene therapy helps decelerate aging process
February 20, 2019 - Study suggests new treatment strategy for deadly brain cancer
February 20, 2019 - Scientists develop unique hybrid implant that imitates bone structure
February 20, 2019 - Push-ups can be tailored to meet specific needs of individuals
February 20, 2019 - Early-career job loss has long term health implications
February 20, 2019 - CVD Does Not Modify Depression-Mortality Link in Elderly
February 20, 2019 - Electrical activity early in fruit flies’ brain development could shed light on how neurons wire the brain
February 20, 2019 - Machine learning technique helps predict which asthma patients respond to corticosteroid therapy
February 20, 2019 - Self-reported sleep duration is a useful tool to measure sleep in children, study suggests
February 20, 2019 - T-cells play key role in how the body fights follicular lymphoma
February 20, 2019 - Study shows how 3D organization of genetic material helps perpetuate the species
February 20, 2019 - Researchers engineer stem cell with ‘suicide genes’ to induce cell death in all but beta cells
February 20, 2019 - Study reveals major sex differences in management of cardiovascular risk factors among U.S. adults
February 20, 2019 - Health Tip: Get Your Child to School on Time
February 20, 2019 - Shortcut strategy for screening compounds with clinical potentials for drug development
February 20, 2019 - Common acid reflux drugs tied to elevated risk for kidney disease
February 20, 2019 - Microbiome could be culprit when good drugs do harm
February 20, 2019 - Prenatal exposure to forest fires causes stunted growth in children
February 20, 2019 - Gene therapy restores hearing in mice with congenital genetic deafness
February 20, 2019 - First molecular test predicts treatment response for kidney cancer
February 20, 2019 - New method for improved visualization of single-cell RNA- sequencing data
February 20, 2019 - Researchers capture altered brain activity patterns of Parkinson’s in mice
February 20, 2019 - A possible blood test for detecting Alzheimer’s disease before symptoms show
February 20, 2019 - Primary care physicians associated with longevity, new research finds
February 19, 2019 - New study identifies many key lessons to establish sanctioned safe consumption sites
February 19, 2019 - Single CRISPR treatment can safely and stably correct genetic disease
February 19, 2019 - Multinational initiative to study familial primary distal renal tubular acidosis
February 19, 2019 - Breakthrough study highlights the promise of cell therapies for muscular dystrophy
February 19, 2019 - Subsymptom Threshold Exercise Speeds Concussion Recovery
February 19, 2019 - Midline venous catheters – infants: MedlinePlus Medical Encyclopedia
February 19, 2019 - Searching for side effects
February 19, 2019 - Humanity is all right, probably, although human extinction remains quite possible, researcher says
February 19, 2019 - Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows
February 19, 2019 - Anti-cancer immunotherapy could be used to fight HIV
February 19, 2019 - Customized Micropatterning for Improved Physiological Relevance
February 19, 2019 - Unique gene therapy approach paves new way to tackle rare, inherited diseases
February 19, 2019 - Activating gene that helps excite neurons reverses depression in male mice
February 19, 2019 - Science Puzzling Out Differences in Gut Bacteria Around the World
February 19, 2019 - Cells that destroy the intestine
February 19, 2019 - On recovery, vulnerability and ritual: An exhibit in white
February 19, 2019 - Scientific Duo Gets Back To Basics To Make Childbirth Safer
Scientists point to potentially promising treatment target for deadly brain cancers

Scientists point to potentially promising treatment target for deadly brain cancers

image_pdfDownload PDFimage_print

Scientists report finding a potentially promising treatment target for aggressive and deadly high-grade brain cancers like glioblastoma. But they also say the current lack of a drug that hits the molecular target keeps it from being advanced for testing as a therapeutic strategy for patients with few treatment options.

Publishing their data online June 18 in Nature Cell Biology, researchers at the Cincinnati Children’s Cancer and Blood Diseases Institute point to a protein that helps regulate cell metabolism called AMPK (AMP-activated protein kinase). Their data suggest AMPK is a key driver of the mostly untreatable brain cancers, and blocking it may produce therapeutic benefit for very ill patients.

But the finding also challenges the scientific status quo regarding AMPK. This is because current research literature characterizes it as a cancer suppressor, according to the study’s senior investigators, Biplab Dasgupta, PhD, and first author Rishi Raj Chhipa, PhD-;both scientists in the Division of Oncology at Cincinnati Children’s.

“AMPK is considered to play a suppressive role in cancer because it inhibits cancer-promoting enzymes like mammalian target of rapamycin (mTOR) and acetyl Co-A carboxylase (ACC),” Dasgupta said. “Our study uses analysis of The Cancer Genome Atlas to show that AMPK proteins are highly expressed in lethal human glioblastoma, that inhibiting AMPK by genetic means shrinks brain tumors and prolongs survival in mice. It also shows that deleting AMPK from the whole body of adult mice is safe for the animals.”

The Cancer Genome Atlas is a collaboration between the National Cancer Institute (NCI) and the National Human Genome Research Institute that has generated comprehensive, multi-dimensional maps of the key genomic changes in 33 types of cancer. According to the NCI, the database is publicly available, making it helpful to the cancer research community to improve the prevention, diagnosis, and treatment of cancer.

Although data in the current study support the feasibility of using pharmacological inhibitors of AMPK to treat glioblastoma, years of additional research are needed before it will be known if the findings are clinically relevant. “We are hopeful our studies will encourage pharmaceutical companies to screen for AMPK inhibitors,” Dasgupta said.

Investigators are planning the next research phases that will be needed to translate the findings to patient care. Dasgupta explained that fostering research collaborations with companies or other institutions with expertise in developing pharmaceutical compounds would help advance the potential therapeutic strategy.

Molecular Hijacking

Cancer cells-;high-grade brain cancer cells in particular-;manage to survive in a highly stressful tumor environment. But the tumor cells maintain their ability to aggressively expand. Although medical science has been able to leverage this stress in part to find effective treatments for a large number of cancers, high-grade brain cancers like glioblastoma remain especially stubborn survivors, defying every treatment strategy thrown at them.

But the current study’s authors found that cancer-associated stress chronically activates AMPK, which normally works as a bioenergetic sensor that helps regulate cell metabolism and stress. They also learned that brain tumor cells hijack a molecular stress- and metabolism-management process regulated by AMPK to help cancer cells maintain their survival abilities.

After discovering this, Dasgupta and colleagues genetically deleted AMPK in human glioblastoma cells and transplanted them into mouse brains. Tumors grew, but very slowly and this prolonged the animals’ survival. “It remains to be seen if inhibiting AMPK in combination with standard of care therapy prolongs survival even further.”

Cancer Evolution

In the course of their research, Chhipa and Dasgupta observed something critical they said could change the way scientists interpret data from cell culture models. The observation also underscores how high-grade brain gliomas are able to evolve genetically to evade targeted molecular treatments, according to the scientists.

They noticed that while AMPK was necessary for the survival of patient-derived stem-like cancer cells recently derived from fresh cancer tissue, the protein was not required for the survival of traditional glioblastoma cell lines cultured for decades.

“Decades of culture could have altered genetic, epigenetic and metabolic characteristics of the lines, which adapted AMPK-independent survival pathways,” said Dasgupta.

Because the large majority of cancer research still relies on cell culture models, Dasgupta said that the study’s findings could become important for the research community, particularly when metabolic pathways of cancer cells are investigated.

Source:

https://www.cincinnatichildrens.org/news/release/2018/brain-cancers

Tagged with:

About author

Related Articles