Breaking News
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
December 10, 2018 - Cervical cancer risk is higher in women with positive HPV, but no cellular abnormalities
December 10, 2018 - Combo therapy not needed if low RA disease activity achieved
December 10, 2018 - Novel therapeutic targets based on biology of aging show promise for Alzheimer’s disease
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Eating disorders now a top priority with Australian Government
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
December 9, 2018 - Feds say heroin, fentanyl remain biggest drug threat to US
December 9, 2018 - Eliminating microglia can reverse some aspects of stress sensitization, study shows
December 9, 2018 - New genetic insight could help treat rare debilitating heart and lung condition
December 9, 2018 - MiRagen Therapeutics Announces Final Safety, Biodistribution and Clinical Efficacy Data From Phase 1 Cobomarsen Clinical Trial in Patients With Mycosis Fungoides
December 9, 2018 - Work with your doctor to weigh pros, cons of treatment options for hyperthyroidism
December 9, 2018 - CWRU researcher secures $14.6 million funding for genetic study into Alzheimer’s disease
December 9, 2018 - High intensity statin treatment and adherence could save more lives
December 9, 2018 - Surgery patients use only 1/4 of prescribed opioids, and prescription size matters
December 9, 2018 - AXT offers Phi Optics upgrade to QPI systems for inverted light microscopes
December 9, 2018 - New booklet could help improve conditions of young pupils with albinism
December 9, 2018 - Few Physicians Work in Practices That Use Telemedicine
December 9, 2018 - Older Adults and Oral Health
December 9, 2018 - Health utility values improve after septorhinoplasty
December 9, 2018 - New EU-funded project provides insight into how the brain develops
December 9, 2018 - Expanded use of tele-emergency services can help strengthen rural hospitals
December 9, 2018 - Infections in the Young May Be Tied to Risk for Mental Illness: Study
December 9, 2018 - Profile: Native Hawaiians and Pacific Islanders
December 9, 2018 - Snoring poses greater cardiac risk to women
December 9, 2018 - Researcher takes further steps in understanding how and why cute aggression occurs
December 9, 2018 - Researchers create new light-activated tools for controlling neurons
December 9, 2018 - Spinal cord injury disrupts the body’s internal clock, study shows
December 9, 2018 - Babies recognize nested structures similar to our grammar
December 9, 2018 - UT Austin researcher receives $2.5 million CZI grant for neurodegenerative disease research
December 9, 2018 - Sleep problems found to be prevalent and increasing among college students
December 9, 2018 - Study reveals why some children are susceptible to the effects of maltreatment
December 9, 2018 - Study investigates influence of different opioids on driving performance
December 9, 2018 - Jazz Pharmaceuticals Announces First Patient Enrolled in Phase 3 Clinical Trial Evaluating JZP-258 for the Treatment of Idiopathic Hypersomnia
December 9, 2018 - Eliminating microglia prevents heightened immune sensitivity after stress
December 9, 2018 - Boys with social difficulties are at greatest risk of early substance use
December 9, 2018 - ‘Wrong’ connective tissue cells linked to worse prognosis in breast cancer patients
December 8, 2018 - Chronic, refractory schizophrenia patients benefit from targeted cognitive training
December 8, 2018 - Advertising in kids’ apps more prevalent than parents may realize
December 8, 2018 - New way to trace the transmission histories of rare genetic diseases
December 8, 2018 - ASH: A+CHP Bests CHOP for Peripheral T-Cell Lymphoma
December 8, 2018 - Results of pediatric genomic epilepsy tests often reclassified
December 8, 2018 - New way of controlling HIV latency to completely eradicate the virus
December 8, 2018 - Phasefocus to showcase the Livecyte 2 at ASCB
December 8, 2018 - KHN’s ‘What the Health?’ Is health spending the next big political issue?
December 8, 2018 - Mussels take in microplastic pollution fibers and flush most of them out again
December 8, 2018 - AHA: How to Stop Smoking … for Good
Study warns that potential epigenetic therapy may boost lung cancer stem cells

Study warns that potential epigenetic therapy may boost lung cancer stem cells

image_pdfDownload PDFimage_print

Epigenetic therapies — targeting enzymes that alter what genes are turned on or off in a cell — are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant. Researchers at Boston Children’s Hospital now report that at least one epigenetic therapy that initially looked promising for lung cancer actually has the opposite effect, boosting cancer stem cells that are believed to drive tumors. They also identify a strategy that reduces these cells, curbing lung cancer in mice.

Findings were published online today in Nature Communications.

Cancer stem cells have been identified in blood cancers and a variety of solid tumors. They make up a tiny fraction of tumor cells, but can regenerate a cancer on their own. Carla Kim, PhD, and colleagues in Boston Children’s Hospital’s Stem Cell Research program have shown that cancer stem cells play a role in adenocarcinoma, the most common type of lung cancer. When they transplanted cancer stem cells from a diseased mouse, previously healthy mice developed lung cancer.

The new study, led by lab member Samuel Rowbotham, PhD, looked at an epigenetic therapy that inhibits the enzyme G9a, a type of histone methyltransferase. G9a had been thought to be cancer-promoting, and some studies have suggested that inhibiting G9a is an effective strategy in certain cancers, including adenocarcinoma. Rowbotham and Kim now call this into question.

“People had looked at cell lines from lung tumors and found that they are sensitive to drugs inhibiting G9a,” says Rowbotham, first author on the paper. “In general tumor cell populations, these drugs would slow down growth or even kill the cells. But we found that these drugs were also making the surviving tumor cells more stem-like. We predicted that this would advance disease progression, and this is what we saw.”

The team first looked at adenocarcinoma cell lines and found that when the cells were treated with G9a, they became more like stem cells. They then transplanted cancer stem cells into live mice and tracked the development of adenocarcinoma. When they knocked down the G9a gene in lung tumors, the tumors grew bigger and spread farther.

Kim believes this down side to G9a hadn’t been noticed because prior studies only looked at cell lines, and because cancer stem cells are hard to detect.

“Earlier studies couldn’t see that cancer stem cells were still around, and there’s more of them when you treat with these drugs,” she says. “Because they’re such a small fraction of the tumor, anything that affects them can easily be missed.”

A new epigenetic target?

But Rowbotham, Kim and colleagues also found potentially better enzymes to target: Histone demethylases. Their action is chemically opposite to that of G9a, stripping off a methyl group from histone where G9a adds one. When Rowbotham knocked down the gene for demethylase enzymes, and added drug that prevents them from working, he was able to make the cells look less like cancer stem cells in a dish and behave less like cancer stem cells in live mice. When he gave demethylase inhibitors to mice with established lung tumors, cancer progression was slowed and the animals survived longer than untreated mice.

Although a cancer stem cell hasn’t been found in human adenocarcinoma, Kim believes the findings are worth pursuing further. She notes a related line of evidence — a 2017 study that found that demethylase inhibitors were effective in killing chemotherapy-resistant cells from patient tumors.

“Even if we can’t pinpoint cancer stem cells in human patients, Sam’s work shows you can start by studying a cancer stem cell in a mouse model and identify targets that could be clinically important,” she says. “It shows the importance of finding the right molecule the cancer is sensitive to. In adenocarcinoma, a demethylase inhibitor is likelier to be more useful than methyltransferase inhibitor.”

They and others envision a two-phase strategy for adenocarcinoma that would first target the general population of cancer cells to “debulk” the tumor, then add a second treatment specifically directed at cancer stem cells.

The team is now doing further studies to explore demethylase inhibitors as potential therapeutic drugs, alone or in combination with other treatments. Because demethylase inhibitors have very broad effects, they will also look for genes the inhibitors affect downstream, which could provide more specific drug targets.

Source:

http://www.childrenshospital.org/

Tagged with:

About author

Related Articles