Diffuse Intrinsic Pontine Glioma : Clinical Features, Molecular Genetics, and Novel Targeted Therapeutics.
Ryan K. Mathew,James T. Rutka +1 more
TL;DR: A clinical overview of DIPG is provided, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery are provided.
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Abstract: Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.
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Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas.
TL;DR: It is speculated that the aberrant activation and/or deactivation of some of the key components of DDR may be synthetically lethal to H3K27M mutation and thus can open novel avenues for effective therapeutic interventions for patients suffering from this deadly disease.
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Advances in NK cell therapy for brain tumors
Jawad Fares,Zachary Davis,Julian S Rechberger,Stephanie A. Toll,Jonathan Schwartz,David J. Daniels,Jeffrey S. Miller,Soumen Khatua +7 more
TL;DR: In this paper , the mechanisms by which the brain tumor microenvironment suppresses NK cell mediated tumor control, and the methods being used to create NK cell products that subvert immune suppression are explored.
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Epigenomics and immunotherapeutic advances in pediatric brain tumors
Malak Abedalthagafi,Nahla Ali Mobark,May Alrashed,Musa Alharbi +3 more
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TL;DR: In this article, the authors focus on primary malignant brain tumors in children and genetic, epigenetic, and molecular characteristics that differentiate them from adults, and discuss the advancements in novel molecularly targeted drugs and how they are being integrated with standard therapy to improve the classification and outcomes of pediatric brain tumors.
Global activation of oncogenic pathways underlies therapy resistance in diffuse midline glioma
Maria-Magdalena Georgescu,Mohammad Zahidul Islam,Yan Li,M. L. Circu,J. Traylor,Christina Notarianni,Cassie Kline,Dennis K. Burns +7 more
TL;DR: This integrated comprehensive analysis revealed a complex spatiotemporal evolution in diffuse intrisic pontine glioma, recommending pontine and cerebellar biopsies for accurate populational genetic characterization, and delineated common signaling pathways and potential therapeutic targets.
Zebrafish Cancer Avatars: A Translational Platform for Analyzing Tumor Heterogeneity and Predicting Patient Outcomes
Majd A. Al-Hamaly,Logan T. Turner,Angelica Rivera-Martinez,Analiz Rodriguez,Jessica S. Blackburn +4 more
TL;DR: Zebrafish are emerging as a time-efficient and cost-effective cancer avatar model and discuss the unique features of zebrafish that make them ideal for the interrogation of cancer heterogeneity and as part of precision cancer medicine pipelines as mentioned in this paper .
References
Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma.
TL;DR: Cooperation of studies incorporating all of these modeling systems to both investigate the unique mechanisms of gliomagenesis in the brainstem and to test potential novel therapeutic agents in a preclinical setting will result in improvement in treatments for DIPG patients.
A standardized autopsy procurement allows for the comprehensive study of DIPG biology.
Madhuri Kambhampati,Jennifer P. Perez,Sridevi Yadavilli,Amanda Saratsis,Ashley D. Hill,Cheng-Ying Ho,Eshini Panditharatna,Melissa Markel,Roger J. Packer,Javad Nazarian +9 more
TL;DR: An autopsy protocol for rapid procurement, documenting and storing specimens, and detailed records to facilitate collaborative analysis of DIPG specimens are developed and implemented.
Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study
Kristin A. Bradley,Tianni Zhou,Rene Y. McNall-Knapp,Regina I. Jakacki,Adam S. Levy,Gilbert Vezina,Ian F. Pollack +6 more
TL;DR: Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.
Management of Diffuse Pontine Gliomas in Children: Recent Developments
Rejin Kebudi,Fatma Betul Cakir +1 more
TL;DR: Recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy are discussed, which includes novel therapeutic options in DIPG.
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Pax3 expression enhances PDGF-B-induced brainstem gliomagenesis and characterizes a subset of brainstem glioma.
Katherine L. Misuraca,Kelly L. Barton,Alexander H. Chung,Alexander K. Diaz,Alexander K. Diaz,Simon J. Conway,David L. Corcoran,Suzanne J. Baker,Oren J. Becher +8 more
TL;DR: In this article, a short list of expression changes specific to the brainstem gliomagenesis process, including abnormal upregulation of paired box 3 (Pax3), were identified, and Pax3 expression marks a subset of brainstem progenitor cells, while it is absent from the cerebral cortex, mirroring its regional expression in glioma.
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