Breaking News
January 23, 2019 - Scientists reveal new mechanism that could lead to specific treatment of strokes and seizures
January 23, 2019 - Both educational level and occupational orientation predict mother’s smoking during pregnancy
January 23, 2019 - How to (gently) get your child to brush their teeth
January 23, 2019 - Short-term hospital readmissions for gun injuries cost $86 million a year | News Center
January 23, 2019 - New certified reference material for testing residual solvents in cannabis
January 23, 2019 - Gene-edited chickens could prevent future flu pandemic
January 23, 2019 - Cardiovascular disease risk begins even before birth
January 23, 2019 - Younger patients receiving kidney transplant more likely to live longer, shows data
January 23, 2019 - Skin samples hold early signs of prion disease, research suggests
January 23, 2019 - Researchers discover how body initiates repair mechanisms that limits damage to myelin sheath
January 23, 2019 - Fecal transplant from certain donors better than others
January 23, 2019 - Risk for Uninsurance in AMI Patients Reduced With Medicaid Expansion
January 23, 2019 - Readmissions reduction program may be associated with increase in patient-level mortality
January 23, 2019 - Fostering translation and communication in medicine and beyond
January 23, 2019 - To Fight Fatty Liver, Avoid Sugary Foods and Drinks
January 23, 2019 - TPU scientists develop new implants that double the rate of bone lengthening in kids
January 23, 2019 - New sessions at Pittcon 2019
January 23, 2019 - Insilico to present latest findings in AI for Drug Discovery at 3rd Annual SABPA FTD Forum
January 23, 2019 - Opioid overdose patients can be safely discharged an hour after administration of naloxone
January 23, 2019 - Scientists find bacterial extracellular vesicles in human blood
January 23, 2019 - Researchers gain new insights into development of necrotizing enterocolitis in preemies
January 23, 2019 - Medical expert advises people with epilepsy not to stockpile medicines
January 23, 2019 - Study outlines research priorities for improving pediatric patient care and safety
January 23, 2019 - Bedfont to exhibit NObreath FeNO monitor at Arab Health 2019
January 23, 2019 - Nicotinamide riboside supplementation confers significant physiological benefits to mothers and offspring
January 23, 2019 - Increasing temperatures may help preserve crop nutrition
January 23, 2019 - Many Oncologists in the Dark About LGBTQ Health Needs
January 23, 2019 - Epigenetic change causes fruit fly babies to inherit diet-induced heart disease
January 23, 2019 - Erasing memories could reduce relapse rates among drug addicts
January 23, 2019 - African Americans who smoke cigarettes are more likely to develop peripheral artery disease
January 23, 2019 - Unique data combination helps FinnGen researchers to fund links between genetic factors and health
January 23, 2019 - Parents’ mental health problems associated with reactive attachment disorder in children
January 23, 2019 - Graphene Flagship project studies impact of graphene and related materials on our health
January 23, 2019 - The connection between the Pope and contraceptive pills
January 23, 2019 - Prior dengue infection could protect children from symptomatic Zika
January 23, 2019 - Previous dengue virus infection associated with protection from symptomatic Zika
January 23, 2019 - VISTA checkpoint implicated in pancreatic cancer immunotherapy resistance
January 23, 2019 - The Tiny Camera That Could Revolutionize Cardiovascular Surgery
January 23, 2019 - Peptide isolated from soil fungi has antitumor and antibacterial properties
January 23, 2019 - TGen identifies polio-like virus as potential cause of Acute Flaccid Myelitis outbreak
January 23, 2019 - Migrants and refugees do not bring disease and are at greater health risk themselves says WHO
January 23, 2019 - Examing the effects of menopause in workplace
January 23, 2019 - Enemy number 1 – Air pollution and climate change top of WHO agenda
January 23, 2019 - Two Positive Phase III studies of Tafenoquine for the Radical Cure of Plasmodium vivax Malaria Published in The New England Journal of Medicine
January 23, 2019 - World Trade Center responders at increased risk for head and neck cancers
January 23, 2019 - Low-sugar diet leads to significant improvement in nonalcoholic fatty liver disease in boys
January 23, 2019 - Chaos in bodily regulation can optimize our immune system, finds study
January 23, 2019 - Short, text-based exercises can increase happiness for adults recovering from substance use disorders
January 23, 2019 - Body size may have greater influence on women’s lifespan than men
January 23, 2019 - Groundbreaking tool helps visualize neuronal activity with near-infrared light
January 23, 2019 - Prior dengue immunity in children may be protective against symptomatic Zika
January 23, 2019 - Holocaust survivors with PTSD and their offspring exhibit more unhealthy behavior patterns
January 23, 2019 - Scientists discover new genetic mutations causing inherited deaf-blindness
January 23, 2019 - UC team designs new naloxone-dispensing smart device
January 23, 2019 - Torrent Pharmaceuticals Limited Issues Voluntary Nationwide Recall of Losartan Potassium Tablets, USP and Losartan Potassium and Hydrochlorothiazide Tablets, USP
January 23, 2019 - Brain activity shows development of visual sensitivity in autism
January 23, 2019 - Two hour gap between dinner and sleep is overrated says Japanese research
January 23, 2019 - Fear and embarrassment are causing smear test numbers to plummet
January 23, 2019 - Protein-secreting device implanted in epileptic rats reduces seizures, improves cognition
January 23, 2019 - Reintroduction project recovers current wild population of green turtle in Cayman Islands
January 23, 2019 - Cancer survivors face greater financial burden related to medical bills
January 23, 2019 - PSA screening reduces prostate cancer deaths by 30%
January 23, 2019 - LSTM receives grant to help improve health of people living in informal settlements
January 23, 2019 - Hemochromatosis Mutation Linked to Other Morbidity
January 23, 2019 - Why early diagnosis of autism should lead to early intervention
January 23, 2019 - Aspirin May Lower Stroke Risk in Women with History of Preeclampsia
January 23, 2019 - Exposure to certain chemicals may be linked to decrease in blood pressure during pregnancy
January 23, 2019 - Bowel cancer on the rise among younger Australians
January 23, 2019 - Scientists have reversed memory loss in a mouse model of Alzheimer’s
January 23, 2019 - Defective molecular master switch could lead to age-related macular degeneration
January 23, 2019 - Researchers identify how concussions may contribute to seizures
January 23, 2019 - Short interval between last meal of the day and bedtime may not affect blood glucose levels
January 23, 2019 - Still Too Many Highway Deaths Tied to Speeding
January 23, 2019 - Prenatal valproate exposure linked to increased ADHD risk
January 23, 2019 - Compound identified that may help treat heart failure
January 23, 2019 - Undiagnosed Asthma in Urban Adolescents May Be Common
January 23, 2019 - Study describes metabolism of intestinal microbiota in babies for the first time
January 22, 2019 - Study links concussions to development of epilepsy
January 22, 2019 - Specialist-led hospital bereavement service may help restrain legal action after difficult deaths
January 22, 2019 - Genetic study reveals possible new routes to treating osteoarthritis
New study shows promise of innovative strategy against HER2-driven lung cancers

New study shows promise of innovative strategy against HER2-driven lung cancers

image_pdfDownload PDFimage_print

The HER2 gene is a well-known driver of breast cancer, where changes in this gene are found in about 1-in-5 cases of the disease. HER2 also contributes to about 3 percent of lung cancers, representing about 6,500 patients per year. But while drugs like trastuzumab and lapatinib have proven effective in silencing the action of HER2 in breast cancer, there are currently no approved HER2-targeted therapies for the treatment of lung cancer.

Now, a University of Colorado Cancer Center study presented at the 30th annual EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics shows the promise of an innovative new strategy against HER2-driven lung cancers (with EGFR involvement, which is also a well-known driver of lung cancer). Tarloxotinib, a potent HER2/EGFR inhibitor, is unique in that the drug only becomes active in low-oxygen conditions, such as those commonly found in tumor tissue. By pairing a potent HER2/EGFR inhibitor with a targeting mechanism specific to tumors, researchers show that tarloxotinib is far more active against lung cancer cell lines than even the most successful existing HER2/EGFR inhibitors, with minimal effect on surrounding, healthy tissues.

“We are very excited about this drug. When it’s near healthy cells, it’s inactive; when it’s near tumor cells, it’s very active. This could provide a new therapeutic approach for patients with HER2 lung cancer,” says Robert C. Doebele, MD, PhD, director of the CU Cancer Center Thoracic Oncology Research Initiative. Dr. Doebele is a co-founder of Rain Therapeutics Inc., a clinical stage biotechnology company developing tarloxotinib as its lead drug candidate.

Tarloxotinib is one in a class of anti-cancer agents known as “prodrugs,” in which inactive molecules are transformed by specific conditions inside the body into active molecules. In the case of tarloxotinib, oxygen molecules scavenge electrons from the prodrug to keep it inactive. In the absence of oxygen, tarloxotinib fractures into its active form.

The current study shows that in healthy, high-oxygen tissues, it takes about an hour for the body to clear half of any administered molecules of tarloxotinib; in low-oxygen tumor tissues, the same clearance takes about 80 hours. This makes tarloxotinib about 50 times more active in low-oxygen conditions than it is in normal-oxygen conditions. And low-oxygen conditions, aka “hypoxia,” are a hallmark of cancer, in which the growth of tumor tissue often outpaces the growth of blood vessels needed to supply the tumor with oxygen.

“The problem is that the concentration of HER2/EGFR inhibitor needed to affect HER2/EGFR lung cancer is so high that these drugs have come with too many side effects to be clinically useful. We hope that our approach with this prodrug will solve that problem, delivering the HER2/EGFR inhibitor where it’s needed without compromising function in healthy tissues,” says Adriana Estrada-Bernal, PhD, the study’s first author.

At noon (GMT) on November 13, the group will present data describing the therapeutic effect of tarloxotinib on mouse models of lung cancer. Collaborators at the University of Auckland will present the following additional data:

Tagged with:

About author

Related Articles