Breaking News
December 15, 2018 - Research offers hope for patients with serious bone marrow cancer
December 15, 2018 - Link between poverty and obesity is only about 30 years old, study shows
December 15, 2018 - Mass spectrometry throws light on old case of intentional heavy metal poisoning
December 15, 2018 - BeyondSpring Announces Phase 3 Study 105 of its Lead Asset Plinabulin for Chemotherapy-Induced Neutropenia Meets Primary Endpoint at Interim Analysis
December 15, 2018 - Study finds that in treating obesity, one size does not fit all
December 15, 2018 - Tenacity and flexibility help maintain psychological well-being, mobility in older people
December 15, 2018 - Study reveals role of brain mechanism in memory recall
December 15, 2018 - High levels of oxygen encourage the brain to remain in deep, restorative sleep
December 15, 2018 - Experimental HIV vaccine strategy works in non-human primates, research shows
December 15, 2018 - Genetically modified pigs could limit replication of classical swine fever virus, study shows
December 15, 2018 - FDA Approves Herzuma (trastuzumab-pkrb), a Biosimilar to Herceptin
December 15, 2018 - Cost and weight-loss potential matter most to bariatric surgery patients
December 15, 2018 - Cancer Research UK and AstraZeneca open new Functional Genomics Centre
December 15, 2018 - New research lays out potential path for treatment of Huntington’s disease
December 15, 2018 - Prestigious R&D 100 Award presented to Leica Microsystems
December 15, 2018 - Study shows septin proteins detect and kill gut pathogen, Shigella
December 15, 2018 - Study sheds new light on disease-spreading mosquitoes
December 15, 2018 - 2017 Saw Slowing in National Health Care Spending
December 15, 2018 - Monitoring movement reflects efficacy of mandibular splint
December 15, 2018 - Study supports BMI as useful tool for assessing obesity and health
December 15, 2018 - Self-guided, internet-based therapy platforms effectively reduce depression
December 15, 2018 - Organically farmed food has bigger climate impact than conventional food production
December 15, 2018 - Faster, cheaper test has potential to enhance prostate cancer evaluation
December 15, 2018 - Researchers study abnormal blood glucose levels of patients after hospital discharge
December 15, 2018 - Swedish scientists explore direct association of dementia and ischemic stroke deaths
December 15, 2018 - Study finds 117% increase in number of dementia sufferers in 26 years
December 15, 2018 - Eczema Can Drive People to Thoughts of Suicide: Study
December 15, 2018 - Link between neonatal vitamin D deficiency and schizophrenia confirmed
December 15, 2018 - Nurse denied life insurance because she carries naloxone
December 15, 2018 - Ritalin drug affects organization of pathways that build brain networks used in attention, learning
December 15, 2018 - Research pinpoints two proteins involved in creation of stem cells
December 15, 2018 - Gut bacteria may modify effectiveness of anti-diabetes drugs
December 15, 2018 - Breast cancer protection from pregnancy begins many decades later, study finds
December 15, 2018 - How often pregnant women follow food avoidance strategy to prevent allergy in offspring?
December 15, 2018 - Using machine learning to predict risk of developing life-threatening infections
December 15, 2018 - How imaginary friends could boost children’s development
December 15, 2018 - Folate deficiency creates more damaging chromosomal abnormalities than previously known
December 15, 2018 - Study provides new insights into molecular mechanisms underlying role of amyloid in Alzheimer’s disease
December 15, 2018 - For the asking, a check is in the mail to help pay for costly drugs
December 15, 2018 - UA scientists uncover biological processes leading to rare brain disorder in babies
December 15, 2018 - The largest database on industrial poisons
December 15, 2018 - ESMO Immuno-Oncology Congress showcases novel technologies set to benefit many cancer patients
December 15, 2018 - Ovid Therapeutics Announces Plans to Move into a Phase 3 Trial in Pediatric Patients Based on End-of-Phase 2 Meeting for OV101 in Angelman Syndrome
December 15, 2018 - Left ventricular noncompaction – Genetics Home Reference
December 15, 2018 - Children’s sleep not significantly affected by screen time, new study finds
December 15, 2018 - When should dementia patients stop driving? A new guidance for clinicians
December 15, 2018 - Researchers use INTEGRA’s VIAFLO 96/384 to streamline the experimental workflow
December 15, 2018 - Researchers discover protein involved in nematode stress response
December 15, 2018 - Cancer patients have greater risk of developing shingles, study shows
December 14, 2018 - UAlberta scientists identify biomarkers for detecting Alzheimer’s disease in saliva samples
December 14, 2018 - Study uncovers link between tube travel and spread of flu-like illnesses
December 14, 2018 - Caffeine plus another compound in coffee may fight Parkinson’s disease
December 14, 2018 - GW researchers review studies on treatments for prurigo nodularis
December 14, 2018 - Lack of peds preventive care ups unplanned hospital admissions
December 14, 2018 - Miscarriage: When Language Deepens Pain
December 14, 2018 - New method helps better understand pathological development of ALS
December 14, 2018 - Intellectually active lifestyle confers protection against neurodegeneration in Huntington’s patients
December 14, 2018 - Mammalian collagen nanofibrils become stronger and tougher with exercise
December 14, 2018 - Considerable Morbidity, Mortality Due to Animal Encounters
December 14, 2018 - Researchers find inhibiting one protein destroys toxic clumps seen in Parkinson’s disease
December 14, 2018 - How early physical therapy can lessen the long-term need for opioids
December 14, 2018 - Depression, suicide rates highest in Mountain West states
December 14, 2018 - New model could cure the potential to underestimate how quickly diseases spread
December 14, 2018 - Exercise-induced hormone activates cells critical for bone remodeling in mice
December 14, 2018 - Researchers discover new mechanism behind spread of malignant pleural mesothelioma
December 14, 2018 - Health Tip: Celebrate a Healthier Holiday
December 14, 2018 - Scalpel-free surgery enhances quality of life for Parkinson’s patients, study finds
December 14, 2018 - Early physical therapy can reduce risk, amount of long-term opioid use | News Center
December 14, 2018 - Genetic marker, predictor of early relapse in common childhood cancer discovered
December 14, 2018 - Study could lead to a potential new way of treating sepsis
December 14, 2018 - New protein complex helps embryonic stem cells to maintain their indefinite potential
December 14, 2018 - Salk professor receives $1.8 million from NOMIS Foundation for research on mechanisms to promote health
December 14, 2018 - New discovery will improve the safety and predictability of CRISPR
December 14, 2018 - Geneticists discover how sex-linked disorders arise
December 14, 2018 - New method to visualize small-molecule interactions inside cells
December 14, 2018 - Study describes mechanism that makes people more vulnerable to hunger-causing stimuli
December 14, 2018 - Chronic opioid therapy associated with increased healthcare spending and hospital stays
December 14, 2018 - Blood Types
December 14, 2018 - Obesity linked to increased risk of early-onset colorectal cancer
December 14, 2018 - Blood test helps identify distinct molecular signatures in children with cystic fibrosis
Cervical tumors may be vulnerable to therapies that attack cancer’s fuel supply, study shows

Cervical tumors may be vulnerable to therapies that attack cancer’s fuel supply, study shows

image_pdfDownload PDFimage_print

Cancer therapies have improved — in some cases dramatically — over the past two decades, but treatment for cervical cancer has remained largely unchanged. All patients receive radiation and chemotherapy, yet despite the aggressive approach, the regimen fails in about one-third of patients with cervical cancer that has spread beyond the cervix but not outside the pelvis.

Now, researchers at Washington University School of Medicine in St. Louis have shown that cervical tumors that don’t respond to radiation may be vulnerable to therapies that also attack the cancer’s fuel supply. Studying mice implanted with human cervical cancer cells, the investigators wiped out many of the animals’ tumors with a combination of radiation and three drugs that target tumor metabolism. They chose drugs that cut off the cancer’s ability to burn glucose and shut down protective processes that help cancer cells survive.

The study is published online in the journal Cancer Research.

“Cancer cell metabolism is a little bit peculiar,” said senior author Julie K. Schwarz, MD, PhD, an associate professor of radiation oncology. “Tumor cells take up glucose faster and in higher amounts than normal tissues. In past imaging studies, my colleagues and I noticed that cervical tumors that took up a lot of glucose prior to radiation treatment tended to be more resistant to radiation therapy than other tumors. If consuming a lot of sugar makes them resistant, we wondered what happens if we inhibit their sugar uptake.”

Schwarz and her colleagues used three different drugs, alone and in combination, to deprive cervical tumors of glucose and block downstream metabolic pathways that help protect cancer cells from building up toxic free radicals. Two of the drugs are investigational and approved by the Food and Drug Administration (FDA) for use in people as part of clinical trials; the third drug is FDA-approved to treat rheumatoid arthritis.

The researchers tested the drug combinations against four different human cervical cancer cell lines. One of the cell lines was vulnerable to being cut off from glucose alone, but the others needed more interference. All four cancer cell lines responded significantly to radiation plus the three-drug combination. One cell line was wiped out entirely. Schwarz and her team noted that the mice did not show obvious negative side effects of this therapy, likely because healthy cells don’t rely on one fuel production pathway.

When Schwarz and her colleagues cut off glucose, they force a cancer cell to scavenge for an alternative fuel. With the tumor in this vulnerable state, the researchers strike again by shutting down the cell’s ability to mitigate the toxic stew it creates from its own deranged metabolism. The treatment essentially forces the cell to drown in its own toxicity, according to the researchers.

“In many cases, when you cut off glucose alone, the cancer cells find ways to compensate,” said first author Ramachandran Rashmi, PhD, a staff scientist in radiation oncology. “But if you then hit their metabolic pathways in two more ways at the same time, the cell can’t recover from that. The stress from the toxic free radicals will escalate, eventually overwhelming the cell.”

Schwarz said that historically, cervical cancer is difficult to study in the lab because most cases are caused by human papillomavirus (HPV), and there is no equivalent infection in mice.

“Ninety to 95 percent of cervical cancer cases are HPV-related, and there are very few studies of this type of cancer in mice because HPV is a human virus,” Schwarz said. “It’s very difficult to produce a mouse model of a solid tumor of the type we see in most women who are diagnosed with cervical cancer. Even though this is a relatively rare cancer, we know HPV is important in a number of other tumors, including those of the head and neck. We believe what we learn from studying cervical cancer will help improve treatments for any HPV-driven cancer.”

Source:

Cutting off cervical cancer’s fuel supply stymies tumors

Tagged with:

About author

Related Articles