Breaking News
February 19, 2018 - FDA Approves First Blood Test to Detect Concussions
February 19, 2018 - Survival Bump in Bladder Cancer with Keytruda
February 18, 2018 - Scientists describe the mechanism of heart regeneration in the zebrafish
February 18, 2018 - Scientists uncover the structure of microtubule motor proteins
February 18, 2018 - Light-activated cancer drugs without toxic side effects are closer to becoming reality
February 18, 2018 - Pioneering research could provide novel insight into how genomic information is read
February 18, 2018 - Pearls From: David Putrino, PhD
February 18, 2018 - Researchers uncover how cancer stem cells drive triple-negative breast cancer
February 18, 2018 - Morning Break: Anti-Anti-Vaxxers; Private Piercings Prohibited; A Case for Pelvic Massage
February 18, 2018 - Lower-dose radiation effective, safe for HPV+ head and neck cancer after induction chemo
February 18, 2018 - Specialist residential service for adults with autism opens in Swansea
February 18, 2018 - FDA Moves to Limit Loperamide Doses per Package
February 18, 2018 - Alcohol use disorder – Genetics Home Reference
February 18, 2018 - Autism might be better detected using new two-minute questionnaire
February 18, 2018 - Hand hygiene-intervention practices may reduce risk of infection among nursing home patients
February 18, 2018 - Researchers develop most sophisticated mini-livers to date
February 18, 2018 - Obamacare Helped More Young Women Get Prenatal Care: Study
February 18, 2018 - School-Based Program Fails to Dent Kids’ Obesity
February 18, 2018 - Research compares neural activity in children with and without autism spectrum disorder
February 18, 2018 - Poor fitness levels increase the risk dementia, concludes study
February 18, 2018 - Risk Score May Reveal if Kids are Victims of Ill-Treatment
February 18, 2018 - Adding Folic Acid to Corn Masa Flour May Prevent Birth Defects
February 18, 2018 - Acute treatment suppresses posttraumatic arthritis in ankle injury
February 18, 2018 - A Role for Budesonide in Autoimmune Hepatitis?
February 18, 2018 - Lupus patients exhibit altered cell proteins, a discovery with potential implications for diagnostics
February 18, 2018 - Muscle plays vital role in regulating heat loss from the hands
February 18, 2018 - High-tech brain scans can provide new way to define intelligence
February 18, 2018 - Study reveals the association between ultra-processed foods and cancer
February 18, 2018 - Prescription Opioid Use Tied to Higher Pneumonia Risk
February 18, 2018 - A non-invasive method to detect Alzheimer’s disease
February 18, 2018 - Deletion of specific enzyme leads to improvement in memory and cognitive functions
February 18, 2018 - Amyloid protein may be transmitted through neurosurgical instruments, study suggests
February 18, 2018 - Electric brain signals of males and females show differences
February 18, 2018 - American Heart Association commends McDonald’s for offering healthier menu in kids’ meals
February 18, 2018 - Parents Find Kids’ Weight Report Cards Hard to Swallow
February 18, 2018 - Does a Financial Conflict of Interest Ever Expire?
February 18, 2018 - Exercise can improve Alzheimer’s symptoms
February 18, 2018 - Scientists develop green chemistry method to improve pharmaceutical manufacturing efficiency
February 17, 2018 - ‘A Time Clock to a Tissue Clock’ for Acute Stroke Care
February 17, 2018 - Cancer Care Gets Personal | NIH News in Health
February 17, 2018 - Do more youth use or do youth use more?
February 17, 2018 - Eating faster linked to obesity
February 17, 2018 - Who’s Still Smoking? ACS Report Highlights Most Vulnerable Adults
February 17, 2018 - Study of smoking and genetics illuminates complexities of blood pressure
February 17, 2018 - Study reveals new link between bone cells and blood glucose level
February 17, 2018 - Children with reading challenges may have lower than expected binocular vision test results
February 17, 2018 - Mass Shootings Trigger Change for Emergency Medicine
February 17, 2018 - ECMO helps revive woman thought to be drowned
February 17, 2018 - Learning stress-reducing techniques may benefit people with epilepsy
February 17, 2018 - Shedding Pounds Before Weight-Loss Surgery a Smart Move
February 17, 2018 - FDA Approves New Cystic Fibrosis Drug Combo
February 17, 2018 - Augmented Reality helps surgeons to ‘see through’ tissue and reconnect blood vessels
February 17, 2018 - Emotional state affects operation of the entire brain instead of being restricted to specific regions
February 17, 2018 - Apalutamide Slows Metastasis in Prostate Cancer
February 17, 2018 - Kids’ well visits linked to lower appendicitis complications
February 17, 2018 - New NK cell-based immunotherapy effective against several types of leukemia
February 17, 2018 - Producing Super-Swelled Lyotropic Crystals for Drug Development
February 17, 2018 - Pfizer Receives Breakthrough Therapy Designation from FDA for PF-04965842, an oral JAK1 Inhibitor, for the Treatment of Patients with Moderate-to-Severe Atopic Dermatitis
February 17, 2018 - Molecular Imaging Flags Risk of AAA Rupture
February 17, 2018 - Researchers identify risk factors for sleep apnea during pregnancy
February 17, 2018 - More work required to find the right drug dosage for pediatric patients
February 17, 2018 - Factors ID’d That Predict RA Remission with Etanercept
February 17, 2018 - A handout or a hand up? How we judge others guides how we help others
February 17, 2018 - ACR receives grant to focus on projects that reduce health disparities
February 17, 2018 - Pimavanserin Might Be Safer Alternative to Ease Dementia Psychosis
February 17, 2018 - Risks of Lung Screening Seen Outweighing Benefits in Many with Smoking History
February 17, 2018 - The impact of Hurricane Harvey on pregnant moms
February 17, 2018 - Gene editing tool used to detect cancer
February 17, 2018 - Researchers detail molecular atlas of cells that form brain’s blood vessels
February 17, 2018 - TUM scientists observe formation of myelin sheaths around nerve fibers
February 17, 2018 - Worst Flu Season Yet? | Medpage Today
February 17, 2018 - Finding the root cause of bronchiolitis symptoms
February 17, 2018 - Climbing stairs reduces hypertension and strengthens muscles
February 17, 2018 - Nature paper unveils bacterial division
February 16, 2018 - Postoperative pain control following extensive pelvic exenteration
February 16, 2018 - Daré Bioscience, Inc. Enters into License and Collaboration Agreement for a Product with the Potential to Receive the First FDA Approval for Female Sexual Arousal Disorder
February 16, 2018 - Havana Embassy Staff: ‘Concussion Without Concussion’?
February 16, 2018 - Family impact of congenital Zika syndrome likely to last a lifetime
February 16, 2018 - STI Prevention Helped By Also Discussing Pot, Alcohol Use
February 16, 2018 - New method maps the dopamine system in Parkinson’s patients
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