Breaking News
October 18, 2018 - Hundreds of dietary supplements shown to contain unapproved drugs
October 18, 2018 - Active Pharmaceuticals ID’d in >700 Dietary Supplements
October 18, 2018 - Cell death protein also damps inflammation
October 18, 2018 - Health Highlights: Oct. 15, 2018
October 18, 2018 - Largest study of ‘post-treatment controllers’ reveals clues about HIV remission
October 18, 2018 - Bad Blood in Silicon Valley: A conversation with John Carreyrou
October 18, 2018 - ANTRUK’s Annual Lecture sends out message on shortage of funds for antibiotic research
October 18, 2018 - NAM special publication outlines steps to ensure interoperability of health care systems
October 18, 2018 - Novel method uses just a drop of blood to monitor effect of lung cancer therapy
October 18, 2018 - New blood test could spare cancer patients from unnecessary chemotherapy
October 18, 2018 - Training young researchers to work with data volumes arising in the health sector
October 18, 2018 - New Metrohm IC method is reliable and convenient to use for zinc oxide assay
October 18, 2018 - Global AIDS, TB fight needs more money: health fund
October 18, 2018 - Understanding the forces that cause sports concussions
October 18, 2018 - Research points to new target for treating periodontitis
October 18, 2018 - New tool improves assessment of postpartum depression symptoms
October 18, 2018 - From Biopsy to Diagnosis
October 18, 2018 - Sexual harassment and assault linked to worse physical/mental health among midlife women
October 18, 2018 - Stumped by medical school? A Q&A with a learning specialist
October 18, 2018 - Targeting immune checkpoints in microglia could reduce out-of-control neuroinflammation
October 18, 2018 - Autonomic nervous system directly controls stem cell proliferation, study shows
October 18, 2018 - FDA Approves Talzenna (talazoparib) for gBRCAm HER2-Negative Locally Advanced or Metastatic Breast Cancer
October 18, 2018 - Sleeping Beauty technique helps identify genes responsible for NAFLD-associated liver cancer
October 18, 2018 - Many U.S. adults confused about primary care, study shows
October 18, 2018 - UC researcher focuses on light-mediated therapies to target breast cancer
October 18, 2018 - With philanthropic gifts, Stanford poised to make major advances in neurosciences | News Center
October 18, 2018 - Mice study shows antibiotics are not always necessary to cure sepsis
October 18, 2018 - Researchers discover why heart contractions are weaker in individuals with HCM
October 18, 2018 - Participation in organized sport during childhood may have long-term skeletal benefits
October 18, 2018 - Probiotic/antibiotic combination could eradicate drug-resistant bacteria
October 17, 2018 - More Socioeconomic Challenges for Hispanic Women With HIV
October 17, 2018 - 49,XXXXY syndrome – Genetics Home Reference
October 17, 2018 - Scientists uncover possible new causes of Tourette syndrome
October 17, 2018 - Girl undergoes unusual heart surgery after compassionate-use exemption | News Center
October 17, 2018 - Health Issues That Are Sometimes Mistaken for Gluten Sensitivity
October 17, 2018 - Elective induction of labor at 39 weeks may be beneficial option for women and their babies
October 17, 2018 - New smart watch algorithms can accurately monitor wearers’ sleep patterns
October 17, 2018 - Researchers demonstrate epigenetic memory transmission via sperm
October 17, 2018 - FDA, DHS announce memorandum of agreement to address cybersecurity in medical devices
October 17, 2018 - Health Tip: Know the Risks of Chicken Pox
October 17, 2018 - Immunotherapy effective against hereditary melanoma
October 17, 2018 - Researchers reveal new mechanism for how animal cells stay intact | News Center
October 17, 2018 - Alzheimer's Goes Under the Cryo-Electron Microscope
October 17, 2018 - Medicare for all? CMS chief warns program has enough problems already
October 17, 2018 - Metrohm Raman introduces Mira P handheld Raman system
October 17, 2018 - Expanding the knowledge about hippocampus to better understand cognitive deficits in MS
October 17, 2018 - Study of Nigerian breast cancer patients reveals prevalence of aggressive molecular features
October 17, 2018 - Many healthy children may have metabolic risk factors, finds study
October 17, 2018 - A new antibiotic could be a better, faster treatment for tuberculosis
October 17, 2018 - “I will not become a Robot Doctor”: A medical student vows to practice compassion
October 17, 2018 - Study findings may explain sporadic outbreaks of C. difficile infections in hospitals
October 17, 2018 - Purdue researchers develop new chemical process to find better drug ‘fits’ for patients
October 17, 2018 - Yale researchers develop way to attack RNA with small-molecule drugs
October 17, 2018 - New pragmatic study launched to understand the effectiveness of new type 2 diabetes drug
October 17, 2018 - Alnylam Announces Plan to Initiate Rolling Submission of a New Drug Application and Pursue Full Approval for Givosiran
October 17, 2018 - Nine cases of polio-like illness suspected in children in illinois
October 17, 2018 - Eisai enters into agreement with Eurofarma for development and sales of lorcaserin in 17 countries
October 17, 2018 - Patients once thought incurable can benefit from high-dose radiation therapy
October 17, 2018 - Researchers awarded grant to advance testing of experimental heroin vaccine
October 17, 2018 - Researchers examine SSRI use during pregnancy and major gestational malformations
October 17, 2018 - FDA grants Rare Pediatric Disease Designation for Immusoft’s Iduronicrin genleukocel-T
October 17, 2018 - Reliable Respiratory announces acquisition of Attleboro Area Medical Equipment
October 17, 2018 - Study reveals link between childhood abuse and higher arthritis risk in adulthood
October 17, 2018 - Research shows people over 65 are not performing enough physical activity
October 17, 2018 - FDA Approves Liletta (levonorgestrel-releasing intrauterine system) 52 mg to Prevent Pregnancy for up to Five Years
October 17, 2018 - Weight gain after smoking cessation linked to increased short-term diabetes risk
October 17, 2018 - Researchers find opportunity to control salt-sensitive hypertension without exercising
October 17, 2018 - Women not warned about cancer associated with breast implants
October 17, 2018 - Metrohm offers robust handheld Raman analyzer for Defense and Security
October 17, 2018 - Modeling Non-Numerical Data in Systems Biology
October 17, 2018 - Research aims to address health disparities in African-American men
October 17, 2018 - Human and cattle decoys trap outdoor-biting mosquitoes in malaria endemic regions
October 17, 2018 - High Circulating Prolactin Level Inversely Linked to T2DM Risk
October 17, 2018 - Study finds gene variant predisposes people to both Type 2 diabetes and low body weight
October 17, 2018 - Metrohm software products make it easy to comply with ALOCA and ALCOA+ guidelines
October 17, 2018 - Network of doctors identify the cause of 31 new conditions
October 17, 2018 - Notable improvement in brain cancer survival among younger patients but not much for elderly
October 17, 2018 - Scientists shed light on roles of transcription factors, TP63 and SOX2, in squamous cell carcinoma
October 17, 2018 - Costs of Medicare Diabetes Prevention Program may be higher than expected reimbursement
October 17, 2018 - Misuse of prescription opioids or benzodiazepines associated with suicidal thoughts
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