 |
|
Researchers identify promising gene target for neuroblastoma therapy
October 16, 2008BOSTON--Researchers at Dana-Farber Cancer Institute have identified a set of previously unknown mutations in a single gene in 8 percent of neuroblastomas, tumors of the nervous system that occur in young children and account for approximately 15 percent of all childhood cancer deaths.
The discovery is intriguing because a small "targeted" molecule inhibitor caused neuroblastoma cell lines carrying two of the mutations to die when treated in the laboratory. This suggests that when mutations activate the gene, known as ALK, tumors become "addicted" to -- or dependent on -- the mutated gene for their continued growth. Therapies designed to inhibit ALK may offer an effective approach to the disease.
For the research team and Dana-Farber itself, the finding is especially rewarding because funding for the study was provided in part by the Friends for Life Foundation, founded by the parents of a young Dana-Farber patient to support neuroblastoma research.
The study appears in the Oct. 16 issue of the journal Nature. The lead author is Rani George, MD, PhD, and the senior author is A. Thomas Look, MD, both from Dana-Farber.
Using high-powered gene-sequencing technologies, Look and his colleagues found five never-before-identified mutations in ALK in 8 percent of the neuroblastoma tumor samples studied. The mutations were all in a portion of the gene responsible for the enzymatic activity of the ALK "receptor," which transmits growth and survival signals to the cell. Some of the mutations give neuroblastoma cells the ability to proliferate even without the molecules that normally activate the receptor in a highly controlled way, the researchers found.
To see whether such haywire growth can be stopped, investigators mixed a powerful ALK-blocking molecule into batches of test cells whose ALK receptors harbor each of the newly discovered mutations. The small molecule inhibitor, TAE684, halted proliferation and brought on the death of cells with the most common mutation, designated F1174L, as well as cells with another of the mutations.
When investigators treated human neuroblastoma cells harboring the F1174L mutation with TAE684, the responses were just as dramatic as they had been in the test cells. The results were confirmed when researchers used a second technique for shutting down ALK genes with the F1174L mutation.
"Our timing is good because there is a new inhibitor of the ALK receptor that is currently showing promise in clinical trials in adults, and which should be available soon for clinical trials in children," said Look. "We are very hopeful that this drug will have activity in children whose tumors have these mutations. More studies are needed, but we are excited by the possibility that this drug and others like it will represent a major step forward for some children with neuroblastoma."
Dana-Farber Cancer Institute
The study appears in the Oct. 16 issue of the journal Nature. The lead author is Rani George, MD, PhD, and the senior author is A. Thomas Look, MD, both from Dana-Farber.
Using high-powered gene-sequencing technologies, Look and his colleagues found five never-before-identified mutations in ALK in 8 percent of the neuroblastoma tumor samples studied. The mutations were all in a portion of the gene responsible for the enzymatic activity of the ALK "receptor," which transmits growth and survival signals to the cell. Some of the mutations give neuroblastoma cells the ability to proliferate even without the molecules that normally activate the receptor in a highly controlled way, the researchers found.
To see whether such haywire growth can be stopped, investigators mixed a powerful ALK-blocking molecule into batches of test cells whose ALK receptors harbor each of the newly discovered mutations. The small molecule inhibitor, TAE684, halted proliferation and brought on the death of cells with the most common mutation, designated F1174L, as well as cells with another of the mutations.
When investigators treated human neuroblastoma cells harboring the F1174L mutation with TAE684, the responses were just as dramatic as they had been in the test cells. The results were confirmed when researchers used a second technique for shutting down ALK genes with the F1174L mutation.
"Our timing is good because there is a new inhibitor of the ALK receptor that is currently showing promise in clinical trials in adults, and which should be available soon for clinical trials in children," said Look. "We are very hopeful that this drug will have activity in children whose tumors have these mutations. More studies are needed, but we are excited by the possibility that this drug and others like it will represent a major step forward for some children with neuroblastoma."
Dana-Farber Cancer Institute
Neuroblastoma Current Events and Neuroblastoma News RSSChildren's cancer group recommends global evaluation system for neuroblastoma to improve treatment
An international coalition of pediatric cancer physicians and researchers has developed new systems to standardize studies of neuroblastomas across the world.
A double-barreled immune cell approach for neuroblastoma
Adding an artificial tumor-specific receptor to immune system cells called T-lymphocytes that target a particular virus extended and improved the cells' ability to fight a form of childhood cancer called neuroblastoma, said researchers form Baylor College of Medicine and Texas Children's Hospital in a report that appears online today in the journal Nature Medicine.
Scientists close in on method to fight deadly childhood cancer
A multicenter team of researchers, including scientists from the University of Florida, has discovered a way to potentially block the growth of neuroblastoma, a type of cancer responsible for 15 percent of all cancer deaths in children.
Children's National researchers develop novel anti-tumor vaccine
A novel anti-tumor vaccine for neuroblastoma and melanoma developed by scientists and clinicians at Children's National Medical Center in collaboration with investigators from the University of Iowa is showing significant impact on tumor growth in mice.
Experiments could lead to new treatments for neuroblastoma
Neuroblastoma is one of the most devastating diagnoses a child can receive. The cancer's victims average 2 years old when the disease is detected, most often by a parent feeling a lump in a child's abdomen. By then, the disease has often reached an advanced stage, and advanced neuroblastoma kills more than 50 percent of the children in whom it develops, despite aggressive treatment with surgery, chemotherapy and radiation.
Potential viral therapy weapon for difficult cancers is safe and effective in study
Combining a herpes virus genetically altered to express a drug-enhancing enzyme with a chemotherapy drug effectively and safely reduced the size of highly malignant human sarcoma grafted into mice.
Families of children with cancer support human tissue research, study finds
Families of children with cancer support research using tissue samples left over after operations, a new study has found.
New insight into the genetics of brain tumor formation
In a G&D paper published online ahead of its April 1 print publication date, Dr. William Kaelin (Dana Farber Cancer Institute) and colleagues identify a potential new neuronal tumor suppressor.
What change does prokineticin 2/Bv8 have in human hepatocellular carcinoma?
Liver hepatocarcinoma is a highly vascularized cancer, and more and more research is focused on the molecules controlling angiogenesis.
Tumor-targeting viral therapy slows neuroblastoma, malignant peripheral nerve sheath tumors
Researchers in a multi-institutional study led by Cincinnati Children's Hospital Medical Center slowed the growth of two particularly stubborn solid tumor cancers - neuroblastoma and peripheral nerve sheath tumors -without harming healthy tissues by inserting instructions to inhibit tissue growth into an engineered virus.
More Neuroblastoma Current Events and Neuroblastoma News Articles
 | Neuroblastoma Research Trends |
 | Neuroblastoma Neuroblastoma is a medical enigma. As a childhood neoplasm arising from neural crest cells, it is characterized by diverse clinical behaviors ranging from spontaneous remission to rapid tumor progression and death. Although clinical outcome can be predicted to a large extent by the stage of disease and the age at diagnosis, an in-depth understanding of its clinico-pathological behavior, now... |
 | Focus on Neuroblastoma Research Neuroblastoma is a cancer that develops from nerve cells found in several areas of the body. Neuroblastoma most commonly affects children age 5 or younger, though it may rarely occur in older children and adults. Neuroblastoma is the most common cancer in babies. Neuroblastoma develops in tissue that makes up the sympathetic nervous system - the system of nerves that automatically regulates your... |
 | Neuroblastoma: Tumor Biology and Therapy by Carl E. Pochedly The purpose of this book is to provide a comprehensive review of current knowledge and to give a thoughtful assessment of the many complex issues involved in the diagnosis and treatment of this common malignant solid tumor found in children. This up-to-date publication also reviews new concepts in histogenesis and histopathology of neuroblastoma. Divided into three main sections, this work... |
 | The Official Parent's Sourcebook on Neuroblastoma: A Revised and Updated Directory for the Internet Age by Icon Health Publications This book has been created for parents who have decided to make education and research an integral part of the treatment process. Although it also gives information useful to doctors, caregivers and other health professionals, it tells parents where and how to look for information covering virtually all topics related to neuroblastoma (also Neuroblastoma child), from the essentials to the most... |
| Human Neuroblastoma: Recent Advances in Clinical and Genetic Analysis by Gian Tonini | |
 | Neuroblastoma Medical Guide by Qontro Medical Guides The Neuroblastoma Medical Guide is a publication which has been designed to better help readers understand Neuroblastoma. This Qontro Medical Guide has been designed with the reader in mind, and is a useful information source for readers at all levels looking to learn more about Neuroblastoma. The Neuroblastoma Medical Guide is highly recommended for those interested in understanding and learning... |
| Neuroblastoma by Judy S.E. Moyes, V. Ralph McCready, Ann C. Fullbrook | |
| Neuroblastoma | |
 | 21st Century Complete Medical Guide to Childhood Cancer (including Neuroblastoma, Brain, Bone, Blood Cancers, Retinoblastoma, Rhabdomyosarcoma, and others) ... on Diagnosis and Treatment Options by PM Medical Health News This up-to-date and comprehensive CD-ROM provides a superb collection of official Federal government documents on childhood cancer: signs and symptoms, diagnosis, lab tests, treatment and management options, and ongoing clinical research. Every aspect of the disease is thoroughly covered. There is no other reference that is as fast, convenient, and portable - everything you need to know, from the... |
| © 2009 BrightSurf.com |