Breaking News
October 21, 2018 - Report reveals growing impact of cannabis on young people
October 21, 2018 - NSF awards $5 million grant to help scientists magnify societal impact of research
October 21, 2018 - Fertility Rates Down for Each Urbanization Level 2007 to 2017
October 21, 2018 - Genetically engineered 3-D human muscle transplant in a murine model
October 21, 2018 - Moms’ tight work schedules may affect their children’s sleep
October 21, 2018 - AHA: No Direct Link Between Preeclampsia and Cognitive Impairment, Study Finds
October 21, 2018 - Weight loss success linked with active self-control regions of the brain
October 21, 2018 - Scripps researchers successfully test potential new smoking-cessation treatment in rodents
October 21, 2018 - More accurate and less stressful way to measure a baby’s heartbeat
October 21, 2018 - Researchers show better cardiorespiratory fitness leads to longer life
October 21, 2018 - Healthy candies for diabetic patients
October 21, 2018 - Environment impact of microplastics remains unclear
October 21, 2018 - Antibiotics for appendicitis? Surgery often not needed
October 21, 2018 - AHA and AMA recognize more than 800 medical practices, health systems for blood pressure control
October 21, 2018 - Scientists obtain clearest ever image of Ebola virus protein
October 21, 2018 - Study reveals connection between two proteins known to be hyperactive in cancer
October 21, 2018 - Gabapentin Beats Pregabalin for Chronic Sciatica
October 21, 2018 - Cosmetic surgeons offering incomplete information for breast augmentation customers
October 21, 2018 - Chronic sleep disruption in early adult life accelerates AD-related tau pathology
October 21, 2018 - Take 10 for Mindfulness – Drugs.com MedNews
October 21, 2018 - Length of breathing disruption in OSA may be better predictor of mortality risk
October 21, 2018 - ApoE4 gene linked with chronic inflammation increases risk for Alzheimer’s disease
October 21, 2018 - Mother-daughter conflict associated with suicide risk in abused adolescent girls
October 21, 2018 - Scientists molding bacteria into unnatural shapes
October 21, 2018 - High diet quality associated with lower risk of death in colorectal cancer patients
October 21, 2018 - Discharged mental health patients ‘at greater risk of dying’
October 21, 2018 - Research provides insight into neurobiology of aggression and bullying
October 21, 2018 - As billions in tax dollars flow to private Medicaid plans, Who’s minding the store?
October 21, 2018 - Neuroscientists identify brain region that appears to be related to food preference decisions
October 21, 2018 - Deaths related to air pollution in the U.S. decreased by 47% between 1990 and 2010
October 21, 2018 - Study shows correlation between spatial memory and the sense of smell
October 21, 2018 - Increased cardiorespiratory fitness associated with reduced long-term mortality
October 21, 2018 - IU researchers receive $1.55 million from NIH to improve chronic-disease management
October 21, 2018 - Income and wealth affect the mental health of Australians, study shows
October 21, 2018 - Patients with hypertension and psoriasis more often require cardiovascular interventions
October 20, 2018 - Leading hip-hop videos depict use of tobacco and marijuana products, study finds
October 20, 2018 - Dose Range of IV Ketamine for Adjunct Tx of Depression Tested
October 20, 2018 - Infants can distinguish between leaders and bullies, study finds
October 20, 2018 - Mad Cow disease found on Aberdeenshire farm
October 20, 2018 - Study identifies factors associated with prescription opioid misuse among students
October 20, 2018 - Scientists uncover key regulator of mTORC1 in cancer growth
October 20, 2018 - Pounds Regained After Weight-Loss Op Can Tell Your Doc a Lot
October 20, 2018 - Sending parents letters to fight childhood obesity doesn’t work
October 20, 2018 - Supervised aerobic exercise can support major depression treatment
October 20, 2018 - Mindfulness-based program effective for reducing stress in infertile women
October 20, 2018 - Molecule capable of halting and reverting neurodegeneration caused by Parkinson’s disease identified
October 20, 2018 - Midazolam-mediated alterations of PER2 expression may have functional consequences during myocardial ischemia
October 20, 2018 - Sweat bees are ideal for studying the genes underlying social behavior
October 20, 2018 - Weight loss success associated with brain areas involved in self-control
October 20, 2018 - KHN’s ‘What the Health?’ Republicans’ preexisting political problem
October 20, 2018 - Research provides a more complete picture of suffering caused by terrorist attacks
October 20, 2018 - Eradicating Helicobacter pylori infections may be a key treatment for Parkinson’s disease
October 20, 2018 - Breast Cancer as a Dynamic Disease
October 20, 2018 - University of Pittsburgh wins NSF grant for big data research to prevent complications from anesthesia
October 20, 2018 - Skin-to-skin contact may promote attachment between parents and preterm infants
October 20, 2018 - Recommendations Developed to Verify NGT Placement in Children
October 20, 2018 - Weight loss can be boosted fivefold thanks to novel mental imagery technique
October 20, 2018 - Children with autism are more likely to be overweight, obese
October 20, 2018 - Nurses making conscientious objections to ethically-relevant policies lack support
October 20, 2018 - Prion strain diversity may be greater than previously thought
October 20, 2018 - Antidepressant treatment may lead to improvements in sleep quality of patients with depression
October 20, 2018 - Study reports increased risk of death in children with inflammatory bowel disease
October 20, 2018 - Number of Autism Genes Now Tops 100
October 20, 2018 - Total diet replacement programmes are effective for treating obesity
October 20, 2018 - CLARIOstar used for fluorescence measurements on CSIRO’s purpose-built research vessel
October 20, 2018 - People with more copies of AMY1 gene digest starchy carbohydrates faster
October 20, 2018 - Case Comprehensive Cancer Center wins NIH grant to study health disparities
October 20, 2018 - Newly discovered compound shows potential for treating Parkinson’s disease
October 20, 2018 - High rate of non-adherence to hormonal therapy found among premenopausal early breast cancer patients
October 20, 2018 - Immunotherapy medicine found to be effective in treating uveitis
October 20, 2018 - The Pistoia Alliance Calls for Greater Collaboration to Realise Benefits of Innovation and Announces Winners of the 2018 President’s Startup Challenge
October 20, 2018 - Female internists consistently earn less than men
October 20, 2018 - Stanford team looks at dangers of teens’ vaping habits
October 20, 2018 - New approach to understanding cancers will accelerate development of better treatments
October 20, 2018 - LJI and UC San Diego awarded $ 4.5 million as part of NCI’s Cancer Moonshot initiative
October 20, 2018 - School-based HPV vaccination did not increase risky sexual behaviors among adolescent girls
October 20, 2018 - Eye discovery to pave way for more successful corneal transplants
October 20, 2018 - New analysis examines the importance of location in the opioid crisis
October 20, 2018 - Green filters increase reading speed for children with dyslexia
October 19, 2018 - Bariatric Sx Cuts Macrovascular Complications in Obesity, T2DM
Researchers identify vulnerability for glioblastoma subtypes

Researchers identify vulnerability for glioblastoma subtypes

image_pdfDownload PDFimage_print

Glioblastoma, the most common and aggressive form of brain cancer, typically fails to respond to treatment or rapidly becomes drug resistant. In a paper published online in the journal Cancer Cell on November 30, University of California San Diego School of Medicine researchers identified a strategy that pinpoints a genetically distinct subpopulation of patients with glioblastoma that is particularly sensitive to drugs like cilengitide that target a cell adhesion receptor known as integrin αvβ3.

Cilengitide was developed based on early studies by David Cheresh, PhD, Distinguished Professor of Pathology at UC San Diego School of Medicine, and colleagues who demonstrated that αvβ3 expression was linked to the progression of glioblastoma. The drug was tested in clinical trials but production was halted in 2014 when it failed to show significant improvement in overall survival among participants during phase III trials.

“In early trials, cilengitide showed promise as some patients in the trial seemed to respond to the drug and appear to show extended survival,” said Cheresh, associate director of innovation and industry alliances at UC San Diego Moores Cancer Center. “We questioned why these patients responded while most did not. We now know that the people who responded to cilengitide have a unique genetic signature that makes them highly susceptible to this drug. More importantly, we have a molecular understanding as to why these patients respond to this drug.”

Cheresh and an international team of scientists found cilengitide is effective in patient-derived tumor cells of a defined subpopulation with proneural and classical glioblastoma subtypes. The Achilles’ heel for these tumors is their addiction to the expression of the high affinity glucose transporter Glut3 — a known driver of cancer stem cells.

“Dependency on Glut3 is critical — a mere expression of this protein is insufficient. What we saw is that many tumors are not addicted to Glut3 and that’s why response to cilengitide was limited,” said Cheresh. “We found that about 15 percent of patient-derived glioblastoma stem cell models were addicted to Glut3 and therefore attacking these tumors with an αvβ3 inhibitor like cilengitide was effective.”

Cancer stem cells thrive on Glut3, which helps tumor cells take up glucose even in very low glucose environments, such as the brain. Integrin αvβ3 increases glucose uptake in the brain by enhancing Glut3 expression, which is critical for tumor growth among this subpopulation of patients, which is why cilengitide appears to be effective for these tumors.

Armed with this new information, the team reported that, utilizing a gene profile alone, they were able to successfully predict which glioblastoma tumors were sensitive to αvβ3 blockade. Currently, there are a number of αvβ3-targeted strategies in development that could be harnessed to target this vulnerability.

This year, more than 12,000 Americans will be diagnosed with glioblastomas, according to the American Brain Tumor Association. Among them: U.S. Senator John McCain, who announced his diagnosis in July. They are highly malignant. The two-year survival rate is 30 percent.

Standard treatment is aggressive: surgery, followed by chemotherapy and radiation. Yet most tumors recur within six months, fueled by a small population of glioblastoma stem cells that resist and survive treatment, continuing to divide and produce new tumor cells to replace those killed by cancer drugs.

“Using a precision medicine approach, we should be able to look at the genetic signature of a patient’s glioblastoma to identify in advance if the patient will respond to this therapeutic approach. An estimated 15 percent of patients may see a benefit,” said Cheresh. “With an advanced understanding of glioblastoma and cancer stem cells, we now have a therapeutic target and the ability to selectively treat tumors that are susceptible to this intervention.”

While not all glioblastoma patients will benefit, these findings represent a major step in identifying a distinct subpopulation who might respond to this type of drug. The next step would be a clinical trial in which patients were selected based on their genetic profile, said Cheresh. The authors believe this drug might be useful in other types of cancer patients with a similar vulnerability.

Source:

https://health.ucsd.edu/news/releases/Pages/2017-11-30-vulnerability-identified-for-subtypes-of-glioblastoma.aspx

Tagged with:

About author

Related Articles