Article

Children’s Oncology Group 2013 blueprint for research: central nervous system tumors. Pediatr Blood Cancer

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. .
Pediatric Blood & Cancer (Impact Factor: 2.56). 06/2013; 60(6). DOI: 10.1002/pbc.24427
Source: PubMed

ABSTRACT In the US, approximately 2,500 children are diagnosed annually with brain tumors. Their survival ranges from >90% to <10%. For children with medulloblastoma, the most common malignant brain tumor, 5-year survival ranges from >80% (standard-risk) to 60% (high-risk). For those with high-grade gliomas (HGGs) including diffuse intrinsic pontine gliomas, 5-year survival remains <10%. Sixty-five percent patients with ependymoma are cured after surgery and radiation therapy depending on the degree of resection and histopathology of the tumor. Phase II trials for brain tumors will investigate agents that act on cMET, PDGFRA, or EZH2 in HGG, DIPG, or medulloblastoma, respectively. Phase III trials will explore risk-based therapy stratification guided by molecular and clinical traits of children with medulloblastoma or ependymoma. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.

0 Followers
 · 
84 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over time, the systematic evaluation of conventional chemotherapy for the treatment of childhood malignant brain tumors has revealed subtype-specific effectiveness. While having a pivotal role in improving survival for medulloblastoma patients, its activity against other tumors, such as pediatric high-grade glioma, remains disappointing. Today’s clinician faces a dilemma when trying to improve patient outcomes further; escalating traditional treatment is likely to produce only additional morbidity without improving cure, particularly for the very young. The current evolution of genetic and molecular brain tumor research brings with it the hope of establishing novel targeted agents that can either supplement or replace standard chemotherapy to improve patient outcome and minimize toxicity. This article reviews literature from the past year evaluating both conventional chemotherapy and molecular agents for the three most common tumor subgroups; medulloblastoma, glioma (low/high-grade) and ependymoma. Future treatment strategies across North America and Europe are also highlighted.
    03/2013; 2(1):38-49. DOI:10.1007/s40124-013-0033-5
  • [Show abstract] [Hide abstract]
    ABSTRACT: The management of adolescents and young adults with brain tumors, which consist of many different histologic subtypes, continues to be a challenge. Better outcome with a decrease of the side effects of the disease and therapy and improvement of quality of life has been demonstrated in recent decades for some tumors. Significant differences in survival and cure are also observed between adult and pediatric tumors of the same histologic grade. Genetic, developmental, and environmental factors likely influence the type of tumor and response observed, even though no clear pathologic features differentiate these lesions among children, adolescents, and adults. Similarly, treatment strategies are not identical among these populations; most patients receive surgery, followed by radiation therapy and multiagent chemotherapy. Advances in understanding the biology underlying the distribution of tumors in adolescents and young adults may influence the development of prospective trials. A more individualized view of these tumors will likely influence stratification of patients in future studies as well as selection for targeted agents. Accordingly, outcomes may improve and long-term morbidities may decrease.
    Current Oncology Reports 06/2013; 15(4). DOI:10.1007/s11912-013-0329-1 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in genomic technologies have allowed for tremendous progress in our understanding of the biology underlying medulloblastoma, a malignant childhood brain tumour. Consensus molecular subgroups have been put forth by the pediatric neuro-oncology community and next-generation genomic studies have led to an improved description of driver genes and pathways somatically altered in these subgroups. In contrast to the impressive pace at which advances have been made at the level of the medulloblastoma genome, comparable studies of the epigenome have lagged behind. Complementary data yielded from genomic sequencing and copy number profiling has verified frequent targeting of chromatin modifiers in medulloblastoma, highly suggestive of prominent epigenetic deregulation in the disease. Past studies of DNA methylation-dependent gene silencing and microRNA expression analyses further support the concept of medulloblastoma as an epigenetic disease. In this Review, we aim to summarize the key findings of past reports pertaining to medulloblastoma epigenetics as well as recent and ongoing genomic efforts linking somatic alterations of the genome with inferred deregulation of the epigenome. In addition, we predict what is on the horizon for medulloblastoma epigenetics and how aberrant changes in the medulloblastoma epigenome might serve as an attractive target for future therapies. This article is part of a Special Issue entitled: "SI: Epigenetics in Brain Function.
    Neuroscience 07/2013; 264. DOI:10.1016/j.neuroscience.2013.07.030 · 3.33 Impact Factor
Show more