Suchergebnisse

Current and future therapy for BRAF-mutant pediatric glioma
Professor Peter J. Houghton from the Greehey Children's Cancer Research Institute discusses new approaches to pediatric cancer treatment specifically for BRAF-mutant pediatric glioma. Low-grade glioma (LGG) is the most frequently diagnosed brain tumor in children, and although five and ten-year survival is quite high, this does not reveal the toxicity of current therapies. Conventional treatment includes intensive chemo-radiation therapy that can lead to cognitive decline, malignant transformation, and other life-debilitating or -threatening sequelae. (1) The 15-year incidence of adverse outcomes such as blindness, hearing loss, obesity, and hormonal imbalance is 18%, 22%, 53%, and approximately 25%, respectively. Among survivors assessed for intellectual function, 34% had an intelligence quotient (IQ) below average. Treatment-resistant progressive disease is the most common cause of death. (2)

Developing novel therapies for childhood cancers
Dr Peter J Houghton from Greehey Children's Cancer Research Institute discusses the obstacles in developing new treatments for childhood cancers and new approaches in preclinical testing. In my previous article for Open Access Government, I focused on the challenges of developing novel therapies for children with glioma, the most prevalent brain cancer in children. Here, I want to discuss the challenges at the preclinical stage of drug development, an area of research that will be altered significantly by the Research to Accelerate Cures and Equity for Children Act (RACE for Children Act). This U.S. law requires the Food and Drug Agency (FDA) to develop a list of molecular targets and molecular targets of new drugs and biologics in development that are determined to be relevant to pediatric cancers. The objective is to facilitate a more rapid introduction of new drugs into the pediatric cancer armamentarium. The FDA may now require pediatric assessments when molecular targets under FDA review are considered relevant to childhood cancer.

Exploring current and future therapies for childhood astrocytoma
Here, Doctor Peter J Houghton explains current therapies for childhood brain cancer what needs to change to ensure better outcomes for children diagnosed with astrocytoma in the future. Cancer in children is rare, representing less than 1% of all cancers in the U.S. Yet, despite major advances in treating childhood cancer, it remains the major cause of disease-related death in children up to 19 years of age in the U.S. It is estimated that 1 in 285 children will be diagnosed with cancer.

Development of novel therapies for pediatric cancer: Successes and challenges
Peter J. Houghton from Greehey Children's Cancer Research Institute and Mary-Ann Bjornsti from the University of Alabama discuss some of the key challenges in the development of therapies for pediatric cancer care. Despite pediatric cancer being a rare disease, constituting less than 1% of cancers overall, research into developing new effective and less genotoxic therapy is of critical importance. 'Significance' in terms of clinical research, for many, is determined by the number of patients afflicted with a particular cancer type. For example, in the US, there are approximately 150,000 new diagnoses for non-small cell lung cancer annually or about ten times the number of all pediatric cancers diagnosed. However, viewing pediatric cancer from the perspective of life-years saved, one can see that giving a child sixty plus years of good quality life is not only 'significant' but is actually cost-effective from the perspective of societal impact. Further, the burden on families following a cancer diagnosis for their child is enormous, both emotionally and financially. That stated, developing novel, effective new agents for the treatment of childhood cancer poses challenges. For three decades, most therapies for pediatric cancer have relied on chemotherapy, with or without external beam radiation. These treatments are toxic and genotoxic and often lead to secondary malignancies or life-threatening long-term sequelae.

Despite multimodal treatment, long term outcome for patients with Ewing sarcoma is still poor. The second "European interdisciplinary Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies. Ewing sarcoma is characterized by a quiet genome with presence of an EWSR1-ETS gene rearrangement as the only and defining genetic aberration. RNA-sequencing of recently described Ewing-like sarcomas with variant translocations identified them as biologically distinct diseases. Various presentations adressed mechanisms of EWS-ETS fusion protein activities with a focus on EWS-FLI1. Data were presented shedding light on the molecular underpinnings of genetic permissiveness to this disease uncovering interaction of EWS-FLI1 with recently discovered susceptibility loci. Epigenetic context as a consequence of the interaction between the oncoprotein, cell type, developmental stage, and tissue microenvironment emerged as dominant theme in the discussion of the molecular pathogenesis and inter- and intra-tumor heterogeneity of Ewing sarcoma, and the difficulty to generate animal models faithfully recapitulating the human disease. The problem of preclinical development of biologically targeted therapeutics was discussed and promising perspectives were offered from the study of novel in vitro models. Finally, it was concluded that in order to facilitate rapid pre-clinical and clinical development of novel therapies in Ewing sarcoma, the community needs a platform to maintain knowledge of unpublished results, systems and models used in drug testing and to continue the open dialogue initiated at the first two Ewing sarcoma summits. ; We thank Anirah Amber and Nuno Andrade for excellent organization of the meeting. The conference was supported by the European Union's Seventh Framework Programme grants 261743(ENCCA) and 259348 (ASSET). ; Sí