Breaking News
March 23, 2019 - People with peripheral artery disease have lower Omega-3 Index, shows research
March 23, 2019 - Trigger warnings have minimal impact on how people respond to content, shows research
March 23, 2019 - Gilead Announces Data From Two Studies Supporting Further Development of GS-6207, a Novel, Investigational HIV-1 Capsid Inhibitor as a Component of Future Long-Acting HIV Therapies
March 23, 2019 - Selfish genetic elements amplify inflammation and age-related diseases
March 23, 2019 - Study provides new understanding of how the brain recovers from damage caused by stroke
March 23, 2019 - CRISPR/Cas libraries could revolutionize drug discovery
March 23, 2019 - Allergic reaction during pregnancy may alter sexual-development in offspring’s brain
March 23, 2019 - Seeing through a robot’s eyes helps those with profound motor impairments
March 23, 2019 - Recent research shows that ease of breastfeeding after C-section differs culturally
March 23, 2019 - Newly discovered parameters offer more control over efficient release of drugs
March 23, 2019 - ‘De-tabooing’ of abortion- Women would like more support from health care community
March 23, 2019 - Anti-TB drugs can increase susceptibility to Mtb reinfection
March 23, 2019 - New survey indicates need of attention to neglected tropical diseases
March 23, 2019 - Innovative in vitro method to develop easy-to-swallow medicine for children and older people
March 23, 2019 - Sugary drinks could raise risk of early deaths finds study
March 23, 2019 - Lian wins ENGINE grant for stem-cell-based therapy to treat Type 1 diabetes
March 23, 2019 - Overall, Physicians Are Happy and Enjoy Their Lives
March 23, 2019 - Researchers discover how blood vessels protect the brain during inflammation
March 23, 2019 - CDC study shows modest improvement in optimal hospital breastfeeding policy
March 23, 2019 - Family-based prevention program to reduce alcohol use among older teens
March 23, 2019 - Remote monitoring of implanted defibrillators in heart failure patients prevents hospitalizations
March 23, 2019 - Appropriate doffing of personal protective equipment may reduce healthcare worker contamination
March 23, 2019 - Window screens can suppress mosquito populations, reduce malaria in Tanzania
March 23, 2019 - Researchers discover new biomarker for postoperative liver dysfunction
March 23, 2019 - Pregnancy history may be linked to cognitive function in older women, finds study
March 23, 2019 - Study shows ticagrelor is equally safe and effective as clopidogrel after heart attack
March 23, 2019 - FDA Approves First Drug for Postpartum Depression, Zulresso (brexanolone)
March 23, 2019 - New guidelines outline new treatment management for psoriasis
March 23, 2019 - Thermally abused cooking oil may promote progression of breast cancer
March 23, 2019 - High-fructose corn syrup fuels growth of colon tumors in mice
March 23, 2019 - Partnership aims at establishing best practices to promote diversity in clinical trials
March 23, 2019 - New study examines presence of microbes in tap water from residences, office buildings
March 23, 2019 - Early life trauma may affect brain structure, contribute to major depressive disorder
March 23, 2019 - NIH starts clinical trial of drug to treat cravings associated with opioid use disorder
March 23, 2019 - Cervix bacteria, immune factors could be a warning signal of premature birth, reports new research
March 23, 2019 - Worst-ever emergency care performance figures underscore the need to focus on staffing
March 23, 2019 - The Current issue of “The view from here” is concerned with Cancer
March 23, 2019 - Mouse model validates how ‘good’ and ‘bad’ bacteria affect acne
March 23, 2019 - Individual amygdala neurons respond to touch, imagery and sounds
March 23, 2019 - Combination of two topical creams can prevent cancer
March 23, 2019 - Study suggests depression screening when assessing African-Americans for schizophrenia
March 23, 2019 - New electronic support system for choosing drug treatment based on patient’s genotype
March 23, 2019 - First-of-its-kind study provides pregnancy statistics of imprisoned U.S. women
March 23, 2019 - Marinus Pharmaceuticals Initiates Phase 3 Study in Children with PCDH19-Related Epilepsy
March 23, 2019 - Laparoscopy: MedlinePlus Lab Test Information
March 23, 2019 - Shellfish allergies: can they be treated?
March 23, 2019 - Toilet seat heart monitoring system
March 23, 2019 - Researchers identify way to improve common treatment for PTSD
March 23, 2019 - High potency cannabis use linked to psychosis finds study
March 23, 2019 - Evoke Pharma Submits Response to FDA Review Letter for Gimoti NDA
March 23, 2019 - Tracking HIV’s ever-evolving genome in effort to prioritize public health resources
March 23, 2019 - Scientists grow most sophisticated brain organoid to date
March 23, 2019 - ADHD drug raising risk of psychosis
March 22, 2019 - FDA approves brexanolone, first drug developed to treat postpartum depression
March 22, 2019 - Gruesome cat and dog experiments by the USDA exposed
March 22, 2019 - Ball pits used in children’s physical therapy may contribute to germ transmission
March 22, 2019 - Long-term use of inexpensive weight-loss drug may be safe and effective
March 22, 2019 - FDA Approves Sunosi (solriamfetol) for Excessive Daytime Sleepiness Associated with Narcolepsy or Obstructive Sleep Apnea
March 22, 2019 - Anti-Müllerian Hormone Test: MedlinePlus Lab Test Information
March 22, 2019 - Finding the right exercise, diet aids for HIV patients
March 22, 2019 - Health Plans For State Employees Use Medicare’s Hammer On Hospital Bills
March 22, 2019 - Researchers develop new tool for imaging large groups of neurons in living animals
March 22, 2019 - Certain bacteria and immune factors in vagina may cause or protect against preterm birth
March 22, 2019 - Research identifies guidelines for prioritizing hepatitis C treatment in U.S. prisons
March 22, 2019 - Novel breath test could pave new way to non-invasively measure gut health
March 22, 2019 - Pharmaceutical and personal care products may result in new contaminants in waterways
March 22, 2019 - New model could revolutionize the way researchers investigate spread of pathogens
March 22, 2019 - MSU professor receives NSF CAREER grant for biosensor diagnostics
March 22, 2019 - High-fat, high-sugar diet in mouse mothers causes problems in the hearts of offspring
March 22, 2019 - ACC: Catheter Ablation Does Not Cut Mortality, Stroke in A-Fib
March 22, 2019 - Wiedemann-Rautenstrauch syndrome – Genetics Home Reference
March 22, 2019 - Health insurance is not assurance of healthcare
March 22, 2019 - Supporting “curiosity-driven research” at the Discovery Innovation Awards
March 22, 2019 - Must-Reads Of The Week (Some Flying Below The Radar)
March 22, 2019 - Newly engineered nanoscale protein micelles can be tracked by MRI
March 22, 2019 - New model more effective in predicting risk of opioid overdose than traditional models
March 22, 2019 - Mayo Clinic study identifies potential new drug therapy for liver diseases
March 22, 2019 - Pitt engineers win $550,000 NSF CAREER award to develop new intervention for people with ASD
March 22, 2019 - Early discharge does not increase readmission risk for patients after lung surgery
March 22, 2019 - Creating diverse pool of trained scientists to address Alzheimer’s research needs
UA scientists aim to identify drug targets for rare pediatric cancer

UA scientists aim to identify drug targets for rare pediatric cancer

image_pdfDownload PDFimage_print

Rhabdomyosarcoma (RMS) is a rare cancer of the skeletal muscle that primarily affects pediatric patients. After diagnosis, about 3 out of 4 patients are cured with standard treatment. Survival rates drop to 17 percent if the disease comes back (recurs) and to 30 percent if it spreads (metastasizes).

“RMS has among the worst survival statistics for any solid pediatric tumor,” said Justina McEvoy, PhD, assistant professor of molecular and cellular biology at the University of Arizona, and member of the UA Cancer Center and the UA BIO5 Institute. “There is an urgent need to improve therapies for these kids.”

In response, scientists are eager to identify “precision” drugs that can target tumors directly. The most comprehensive assessment of RMS drug targets recently was published in Cancer Cell. Dr. McEvoy, who was a first author, joined the study when she was a postdoctoral fellow at St. Jude Children’s Research Hospital in Memphis, Tenn., and continued to contribute after joining the UA in 2014.

Dr. McEvoy describes a target as a key protein that a drug can attack.

“A target is a protein that instructs the cell to be cancerous. If we could shut that protein down, we could reverse or stop that process,” she said. “Rhabdomyosarcomas have very few druggable mutations, which makes developing treatments difficult.”

To find drug targets, scientists focus on genetic “signaling pathways,” which is a system to relay instructions from one end of the cell to the other to direct growth and division.

“Think of it as a phone tree, where a parent starts calling other parents, and those parents call other parents, and finally they execute a plan,” Dr. McEvoy said. “A signaling pathway ultimately turns on all the machinery needed for the cell to divide.”

Dr. McEvoy and her team sifted through a large genetic and protein database collected for rhabdomyosarcoma to identify pathways containing potential drug targets. They focused on a gene called WEE1, which codes for a protein kinase that regulates cell division and is particularly active in rhabdomyosarcoma. In lab experiments pitting drug candidates against RMS tumor cells, the team found one drug in particular, adavosertib, was especially potent against tumors expressing WEE1, particularly when combined with the chemotherapy drug irinotecan.

“When we combined irinotecan, the current therapy for RMS, with adavosertib, most of the tumors either had a complete or partial response, or stable disease,” Dr. McEvoy reported. “It was pretty effective compared to the standard treatment alone.”

Before adavosertib can be used in RMS patients, scientists must gather more evidence for its effectiveness. Dr. McEvoy’s former team at St. Jude is pushing that research forward. The team’s work also offers a jumping-off point for many additional paths in RMS research. At the UA Cancer Center, Dr. McEvoy is using the same datasets to branch off into her own research niche, focusing on molecules called “non-coding RNAs.”

“Non-coding RNAs are emerging as key regulators in tumor formation,” Dr. McEvoy said. “The work is challenging because nothing is really known about them in rhabdomyosarcoma, but it’s also exciting because it opens a new window of opportunity.”

The genetic code is a tangle of molecules that can be unwound to reveal the score for the symphony of life, each gene signifying a protein, or a note. But many genes don’t make proteins, resulting in a symphony with long periods of silence between movements. It turns out, however, that rather than playing notes, these genes might be conducting the orchestra, directing cells to play some notes at full blast while muting others.

Figuring out how non-coding RNAs function is a relatively new endeavor, and Dr. McEvoy is excited to learn more about how these mysterious sections of the human genome guide the growth of RMS cells, perhaps by activating some genes and deactivating others. Her lab is uncovering how one of the major mutations driving RMS is regulated by non-coding RNAs.

“When we deactivate the non-coding RNA, we can shut off the expression of that mutant gene, and cancer cells in a culture dish die. It’s pretty drastic,” Dr. McEvoy said. “Now we’re trying to understand what other genes and proteins might be regulated by these non-coding RNAs. Our goal is to find already-existing therapies to shut down those pathways.”

Dr. McEvoy knows that science is a marathon, not a sprint, and is motivated by her belief that the hard work ultimately will pay off.

“When I see the pieces coming together, when we can see the potential for therapeutic advancement — it is really rewarding,” she said.

Source:

https://uahs.arizona.edu/

Tagged with:

About author

Related Articles