Breaking News
December 12, 2017 - CAR T cell therapy shows long-lasting remissions in non-Hodgkin’s lymphoma patients
December 12, 2017 - Live-cell microscopy reveals internal forces that direct cell migration
December 12, 2017 - GSK Submits US Regulatory Application for Single-Dose Tafenoquine for Plasmodium vivax Malaria
December 12, 2017 - High Blood Urea Nitrogen Levels Tied to T2D Risk
December 12, 2017 - Blood Smear: MedlinePlus Lab Test Information
December 12, 2017 - Atopic eczema—one size does not fit all
December 12, 2017 - Biological Applications of AFM
December 12, 2017 - Study provides new insights into mechanism of tumor survival in glioblastoma
December 12, 2017 - FDA Approves Admelog (insulin lispro) Short-Acting “Follow-On” Insulin Product to Treat Diabetes
December 12, 2017 - Chromosomes Fact Sheet – National Human Genome Research Institute (NHGRI)
December 12, 2017 - Discovery puts the brakes on HIV’s ability to infect
December 12, 2017 - Researchers uncover novel strategy to program immune system for fighting cancer
December 12, 2017 - Study finds under-age marriage for women as marker of multiple vulnerabilities
December 12, 2017 - Scientists discover specific mechanism of Zika virus-associated microcephaly
December 12, 2017 - Creating Your Family Health Tree
December 12, 2017 - Biological Pathways Fact Sheet – National Human Genome Research Institute (NHGRI)
December 12, 2017 - LSUHealthNO breakthrough may pave way for advances in obesity-related diseases
December 12, 2017 - Few people with HIV get prompt care after incarceration
December 11, 2017 - Air pollution exposure before or after conception linked to increased risk of birth defects in children
December 11, 2017 - Abu Dhabi focuses on reducing childhood obesity
December 11, 2017 - Employees with influenza have more lost work time
December 11, 2017 - type 2 diabetes – Genetics Home Reference
December 11, 2017 - Insufficient evidence to guide recommendations on vitamin D in pregnancy
December 11, 2017 - St. Jude gene therapy offers hope for infants with ‘bubble boy’ disease
December 11, 2017 - Soy foods, cruciferous vegetables may reduce breast cancer treatment’s side effects
December 11, 2017 - Nearly 3 in 10 elite footballers at top clubs have undetected lung and airway problems, study finds
December 11, 2017 - Why some workers can’t call it quits
December 11, 2017 - Healthier Diet, Less Salt: The Recipe to Beat High Blood Pressure: MedlinePlus Health News
December 11, 2017 - Research leads to call for lung health screening at top football clubs
December 11, 2017 - Drug improves disease-free, overall survival after hematopoietic stem cell transplants
December 11, 2017 - Researchers generate 3D cell cultures to investigate mechanisms of drug resistance in breast cancer
December 11, 2017 - New, more easily administered therapies offer benefits for bleeding and clotting disorders
December 11, 2017 - Opioids after surgery left her addicted. Is that a medical error?
December 11, 2017 - Scientists develop software that predicts leukemia-specific immune targets
December 11, 2017 - Does Your Pet Have a Weight Problem? Here’s How to Tell: MedlinePlus Health News
December 11, 2017 - Genetic variant prompts cells to store fat, fueling obesity
December 11, 2017 - Canola oil linked to worsening of Alzheimer’s
December 11, 2017 - New Breast Cancer Drug Ribociclib (Kisqali) May Benefit Younger Women, Too
December 11, 2017 - Healthy Living May Ease Some MS Symptoms: MedlinePlus Health News
December 11, 2017 - Researchers develop a molecular taxonomy for hair disorders
December 11, 2017 - Study shows safety, efficacy of cystic fibrosis drug in children between 1 to 2 years of age
December 11, 2017 - Two immunotherapy approaches for multiple myeloma show hope
December 11, 2017 - The Valley Hospital uses novel mobile app to enhance pre-hospital emergency care
December 11, 2017 - ‘I Entered Medical School Through a Hunger Strike’: What We Heard This Week
December 11, 2017 - Research team unlocks secrets of Ebola
December 11, 2017 - Generic versions of Viagra coming this week
December 11, 2017 - New genetic model identified for predicting outcomes in patients with primary myelofibrosis
December 11, 2017 - Research shows that e-cigarettes serve as gateway to traditional smoking
December 11, 2017 - A risk factor for drug-induced skin disease identified
December 11, 2017 - MIT researchers discover new way to make bacteria vulnerable to existing antibiotics
December 11, 2017 - Dengue vaccine issues in the Philippines
December 11, 2017 - Office Workers Don’t Like Being Chained to Their Desks: MedlinePlus Health News
December 11, 2017 - Study reveals how a very low calorie diet can reverse type 2 diabetes
December 11, 2017 - Study highlights potential for reducing greenhouse gas emissions in health care settings
December 11, 2017 - University of Adelaide receives $23.2 million for preterm birth research
December 11, 2017 - Tough Flu Season Ahead: Vaccine May Only Be 10% Effective
December 11, 2017 - Getting Self-Driving Cars on the Road Soon Might Save Lives: MedlinePlus Health News
December 11, 2017 - Enterovirus vaccine prevents virus-induced diabetes in a T1D experimental model
December 11, 2017 - Solar retinopathy or sun damage to the eyes – a case report
December 11, 2017 - Cancer risk with birth control pills emerges again in latest study
December 10, 2017 - Deer Hunters: Put Safety First: MedlinePlus Health News
December 10, 2017 - High blood pressure is redefined as 130, not 140: US guidelines (Update)
December 10, 2017 - Unusual neuroinflammation may underlie cognitive problems in cART-treated HIV patients
December 10, 2017 - Racial differences in parents’ reports of child’s autism symptoms may contribute to delayed diagnosis
December 10, 2017 - Taurine could boost effectiveness of existing multiple sclerosis therapies
December 10, 2017 - The man with a young woman’s heart
December 10, 2017 - Patient bedside remains important component of medical education for students
December 10, 2017 - Nutrition labeling has little impact on sodium consumption
December 10, 2017 - ‘Obesity paradox’ not present among people with new cases of cardiovascular disease
December 10, 2017 - SLU scientists provide promising approach in designing new drugs for DMD
December 10, 2017 - Can PD-1 Inhibitor Help Eradicate HIV?
December 10, 2017 - Checking Prices for Medical Procedures Online? Good Luck: MedlinePlus Health News
December 10, 2017 - Researchers find bacteria tied to esophageal cancer
December 10, 2017 - Boy’s Double Hand Transplant Changed His Brain
December 10, 2017 - Memo to Doctors: Spit Out the Bad News: MedlinePlus Health News
December 10, 2017 - Two years of extended anastrozole therapy proved as effective as five years in clinical trial
December 10, 2017 - Using digital devices before bed may contribute to sleep and nutrition problems in children
December 10, 2017 - Are You Sure That’s What the Doctor Said About Your Leukemia?: MedlinePlus Health News
December 10, 2017 - Low vitamin D levels at birth linked to higher autism risk
December 10, 2017 - Alcohol use in movies influences onset of drinking among 10- to 15-year-olds
Research findings offer prime drug targets to treat rare liver cancer that strikes young people

Research findings offer prime drug targets to treat rare liver cancer that strikes young people

image_pdfDownload PDFimage_print

After years of rigorous research, a team of scientists has identified the genetic engine that drives a rare form of liver cancer. The findings offer prime targets for drugs to treat the usually lethal disease, fibrolamellar hepatocellular carcinoma (FL-HCC), which mainly strikes adolescents and young adults.

Sanford Simon, who conducted the research as head of The Rockefeller University’s Laboratory of Cellular Biophysics, describes the culprit as a “chimeric gene,” a mutation created when two genes fuse together. These genes normally sit far apart from each other, separated by some 400,000 base pairs, the building blocks of DNA that combine to form genes.

The chimeric gene, which Simon’s lab first characterized three years ago, has been found in each of the hundreds of FL-HCC patients tested for the mutation.

A disease mechanism revealed

Having confirmed the chimeric gene as a hallmark of the disease, Simon set out to explore if and how it may cause these malignant tumors. He worked with Scott Lowe, a cancer geneticist at the Memorial Sloan Kettering Cancer Center, to develop a mouse model of FL-HCC.

In work published this week in the Proceedings of the National Academy of Sciences, the scientists used CRISPR gene editing, a highly precise tool for manipulating DNA, to generate mice that carry the 400,000 base-pair deletion and produce the chimeric gene. Edward Kastenhuber, a graduate student in Lowe’s lab, found that these mice develop liver tumors that mimic the biology of the tumors found in humans with FL-HCC, suggesting that the deletion is in itself sufficient to cause the cancer–other alterations are not necessary for tumors to grow.

However, this experiment left open the question of precisely how the deletion spurs cancer: by eliminating genes that normally would suppress the growth of tumors, or by introducing the chimeric gene. Another experiment, in which mice with the fused gene but no deletion in the genome developed tumors, proved that it’s the mutation, not the missing DNA as such, that causes the disease.

With the chimeric gene firmly established as the driver of the disease, and its cellular mechanisms defined, Simon and his team–including Gadi Lalazar, of Rockefeller’s Clinical Scholars Program, and graduate student David Requena–are now working to identify potential targets for drugs to treat the disease.

New concepts for therapy

Among these drug targets is a protein produced from the fused gene that belongs to a family of enzymes called kinases. These enzymes are often mutated in cancers. “In fact,” Simon explains, “some of the most successful cancer therapies available, including Gleevec, act by targeting specific kinases.”

The researchers showed that disruption of the fused gene’s kinase activity impaired the formation of tumors in mice–a finding that has strengthened their confidence that agents aimed at targeting this activity or its consequences might be effective against FL-HCC.

The team is also studying the effects of targeting a number of cellular signaling systems that have previously been implicated in other cancers, and that speed tumor growth when they become overactive in FL-HCC patients. And they will be using their new mouse model as a system to test the effectiveness of new therapies prior to initiating clinical trials in patients.

Simon first became interested in FL-HCC nine years ago, when his 12-year-old daughter Elana was diagnosed with the disease. (Now 21, Elana is a senior at Harvard, and a lead author on earlier reports characterizing the genomics of the disease.) He continues to embrace the challenge the cancer presents and attributes the latest breakthroughs to an “incredible perfect storm” of advances in all of the sciences, thanks to decades of public investment in basic research.

“Here’s a cancer where, five years ago, we didn’t know if it was one disease or many diseases lumped together,” Simon adds. “We didn’t know if it was inherited or if it was due to a sporadic mutation. And now we know exactly what the driver is and how it works, and we can start designing therapeutics.”

Source:

https://www.rockefeller.edu/

Tagged with:

About author

Related Articles