Molecular mechanisms and therapeutic targets in pediatric brain tumors.

Molecular mechanisms and therapeutic targets in pediatric brain tumors. Sci Signal. 2017 Mar 14;10(470): Authors: Liu KW, Pajtler KW, Worst BC, Pfister SM, Wechsler-Reya RJ Abstract Brain tumors are among the leading causes of cancer-related deaths in children. Although surgery, aggressive radiation, and chemotherapy have improved outcomes, many patients still die of their disease. Moreover, those who survive often suffer devastating long-term side effects from the therapies. A greater understanding of the molecular underpinnings of these diseases will drive the development of new therapeutic approaches. Advances in genomics and epigenomics have provided unprecedented insight into the molecular diversity of these diseases and, in several cases, have revealed key genes and signaling pathways that drive tumor growth. These not only serve as potential therapeutic targets but also have facilitated the creation of animal models that faithfully recapitulate the human disease for preclinical studies. In this Review, we discuss recent progress in understanding the molecular basis of the three most common malignant pediatric brain tumors-medulloblastoma, ependymoma, and high-grade glioma-and the implications for development of safer and more effective therapies. PMID: 28292958 [PubMed - in process]
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research

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Successful use of immune checkpoint inhibitors in a variety of cancers has generated interest in using this approach in pediatric brain tumors. We performed a retrospective review of 10 consecutive children (6 boys, 4 girls; ages, 2 to 17 y), with recurrent or refractory pediatric brain tumors (5 high-grade glioma, 1 low-grade glioma, pineoblastoma, medulloblastoma, ependymoma, and CNS embryonal tumor, NOS) treated at Rady Children’s Hospital San Diego from 2015 to 2017 with the immune checkpoint inhibitor nivolumab (3 mg/kg every 2 wk). Eight of 10 patients received prior chemotherapy and 9 radi...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Original Articles Source Type: research
ConclusionH3 K27M mutations are frequent in adult midline gliomas and have a prognostic role similar to H3 K27M wild-type high-grade tumors.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: H3 K27M mutations are frequent in adult midline gliomas and have a prognostic role similar to H3 K27M wild-type high-grade tumors. PMID: 30610375 [PubMed - as supplied by publisher]
Source: Clin Med Res - Category: Research Authors: Tags: J Cancer Res Clin Oncol Source Type: research
Purpose of review Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors. Recent findings Genome-wide and epigenome-wide profiling data have revealed distinct tumor en...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: HEMATOLOGY AND ONCOLOGY: Edited by Susan M. Blaney Source Type: research
Conclusion: Compared to PFT patients treated with surgery alone, PFT patients treated with chemo-radiotherapy showed lower hippocampal volumes and altered hippocampal growth trajectory. Serial quantitative MRI measures of brain may provide a neuroanatomical substrate for assessing functional impact on normal brain function following treatment of posterior fossa tumours. PMID: 28748803 [PubMed - as supplied by publisher]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
Introduction: The understanding of pediatric CNS tumors biology is essential in the development of disease stratification and in development of less toxic therapeutic agents as well as finding novel markers for early diagnosis. MicroRNAs are short 18-25 nucleotide small non-coding RNA molecules regulate gene expression. Recent studies showed that miRNAs play a significant role in brain tumor biology; and may up-regulated or down-regulated in malignancies, which referred their oncogenic or tumor suppressor effect. MiRNA expression patterns have been linked to clinical outcomes, tumor regulation; such as tumor progression, c...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: RNA Regulons: the Hidden Codes of the Cancer Genome Source Type: research
ConclusionsThe combination of these AKT and mTOR inhibitors was safe and feasible in patients with recurrent/refractory pediatric solid tumors.
Source: Pediatric Blood and Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
Exposure to cranial radiation in childhood increases the risk of subsequent CNS malignancies, an important cause of late mortality. Studies have shown a linear relationship between radiation dose and risk of secondary meningiomas and gliomas. However no studies have specifically examined the development of diffuse intrinsic pontine glioma (DIPG) after childhood craniospinal radiation. Given the frequent brainstem irradiation and growing number of pediatric brain tumor survivors, we sought to investigate the risk of DIPG as a secondary malignancy in childhood cancer survivors. We performed a retrospective analysis of the DI...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: CLINICAL TRIALS AND OUTCOMES - PEDIATRICS Source Type: research
In conclusion, we have demonstrated that a fraction of tumor cells can survive the lengthy period of postmortem anoxia/starvation and regain tumorigenic capabilities in mouse brains; and identified CD57 as a new marker of the therapy-resistant cells. This novel panel of ADOX models should facilitate biological studies and preclinical therapy of pediatric brain tumors.
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MODELS Source Type: research
ConclusionsWe identify common features and individual differences in the systemic immune profiles of children with brain tumors. Overall, patients with MB displayed a uniform cytokine profile, whereas other tumor diagnoses did not predict systemic immunological status in single patients. Future characterization and monitoring of systemic immune responses in children with brain tumors will have important implications for the development and implementation of immunotherapy.
Source: Pediatric Blood and Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
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