Breaking News
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 - 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
December 8, 2018 - Scientists overturn odds to make Parkinson’s discovery
December 8, 2018 - Health benefits of producing marula vinegar
December 8, 2018 - Failure of critical cellular energy sensor responsible for CKD progression, study finds
December 8, 2018 - Ethnicity can be reliable indicator of gut microbiota diversity
December 8, 2018 - Safe Sleep for Baby | NIH News in Health
December 8, 2018 - Study looks at ways technology can support nutritional needs of Parkinson’s patients
December 8, 2018 - Infant milk allergy is being overdiagnosed say experts
December 8, 2018 - Graphene may one day be used to test for ALS
December 8, 2018 - Houston Methodist launches real-time website to track flu cases
December 8, 2018 - RedHill Announces Positive Top-Line Results from Confirmatory Phase 3 Study with Talicia for H. pylori Infection
December 8, 2018 - A way to measure obesity and health beyond BMI
December 8, 2018 - New diagnostic tools may help identify breast cancer patients who could benefit from targeted therapies
December 8, 2018 - Duke-NUS researchers highlight possible role of bioaerosol sampling in pandemic surveillance
December 8, 2018 - Study quantifies links between alcohol, drug use and violent deaths
December 8, 2018 - Mothers’ stress levels at conception linked to child’s response to life challenges at age 11
December 8, 2018 - MIT researchers develop antimicrobial peptides from South American wasp’s venom
December 8, 2018 - Obesity prevention among low-income, diverse preschool-aged children and parents
December 8, 2018 - Mount Sinai researcher awarded $2.5 million to advance understanding of neurodegenerative diseases
December 8, 2018 - CZI announces funding for open-source software efforts to improve image analysis in biomedicine
December 8, 2018 - New book encompasses the vast history of reproduction
December 8, 2018 - Low-income women in Texas are not receiving contraception after childbirth, study shows
December 8, 2018 - Study expands knowledge about sexuality and gender gaps in political attitudes
December 8, 2018 - Drug reduces hot flash frequency, improves quality of life in breast cancer survivors
December 8, 2018 - Imaging, Biopsy Often Still Needed After Mastectomy
December 8, 2018 - Physical Activity Guidelines for Americans: 2nd edition
December 8, 2018 - Machine learning can improve chemical toxicity prediction
Drug used to treat dizziness may slow down growth of triple-negative breast cancer

Drug used to treat dizziness may slow down growth of triple-negative breast cancer

image_pdfDownload PDFimage_print

Screening Food and Drug Administration (FDA)-approved compounds for their ability to stop cancer growth in the lab led to the finding that the drug flunarizine can slow down the growth of triple-negative breast cancer in an animal model of the disease. Led by researchers at Baylor College of Medicine and the National Taiwan University College of Medicine, the team shows in the journal Scientific Reports proof of concept that this approach can potentially lead to the discovery of drugs in a way that is quicker and less expensive than traditional drug development strategies.

“We focused on finding ways to disrupt the effects of a class of protein called Ras, which are powerful drivers of a wide range of cancers. In this proof-of-concept study we have established a strategy to target N-Ras for therapy,” said co-corresponding author Dr. Eric C. Chang, associate professor of molecular and cellular biology and the Lester and Sue Smith Breast Center in the Dan L Duncan Comprehensive Cancer Center at Baylor. “N-Ras drives a form of triple-negative breast cancer, a very aggressive form of cancer for which there is no targeted therapy available. So we thought that, if we could target one of the drivers, we might be able to make a contribution toward finding effective therapies.”

Directly interfering with Ras proteins has proven to be difficult, Chang explains, “but this is important because RAS can drive resistance to other forms of treatments targeting downstream pathways.” Therefore, he and his colleagues sought safe and approved compounds that can reduce the amount of N-Ras in cancer cells by altering the cell’s natural ability to degrade this protein.

“Our assay allows us to visually determine which drugs promote N-Ras degradation,” Chang said. “We tagged N-Ras proteins with a green fluorescent tag. If the fluorescent N-Ras proteins were destroyed, the fluorescence would be lost. These assays were conducted with an automated microscopy system in the laboratory of co-author Dr. Stephen Wong at the Methodist Hospital Research Institute.”

Chang and his colleagues tested a number of FDA-approved compounds on their green cells. The drugs that made the green color disappear were those that degraded N-Ras in the cells and were potential candidates for further testing their effect on cancer growth. Of all the compounds they tested, flunarizine worked best in this test.

A potential new purpose for an old drug

“Flunarizine has been used in medical practice for decades to treat dizziness and vertigo and to prevent migraines,” Chang said. “Our study shows a new function; it also can promote degradation of cancer-promoting N-Ras.”

The researchers also tested the effect of flunarizine in a mouse model of triple negative breast cancer and found that it slowed down tumor growth. They also determined that flunarizine promotes N-Ras degradation by enhancing a natural cellular pathway called autophagy. This pathway was first discovered by the ability to provide cells a way to survive starvation by degrading and recycling cellular materials.

“Screening existing relatively safe drugs for new functions is a valuable strategy for identifying drugs that can potentially be used to treat diseases for which currently there are no available treatments,” Chang said. “Reprograming pathways that degrade cellular materials may be an effective strategy to remove a cancer driver that is otherwise hard to target.”

This study was speared by Ze-Yi Zheng, the first author on this paper. Other contributors to this work include Jing Li, Fuhai Li, Yanqiao Zhu, Kemi Cui, Stephen T. Wong and Yi-Hua Liao. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the Methodist Hospital Research Institute Houston, National Taiwan University Hospital and National Taiwan University College of Medicine in Taiwan, and the Southwest Medical University in China.

Tagged with:

About author

Related Articles