TY - JOUR
T1 - H3K27-altered diffuse midline glioma
T2 - a paradigm shifting opportunity in direct delivery of targeted therapeutics
AU - Rechberger, Julian S.
AU - Power, Blake T.
AU - Power, Erica A.
AU - Nesvick, Cody L.
AU - Daniels, David J.
N1 - Funding Information:
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. No financial or material support was received for this research or the creation of this work.
Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - Introduction: Despite much progress, the prognosis for H3K27-altered diffuse midline glioma (DMG), previously known as diffuse intrinsic pontine glioma when located in the brainstem, remains dark and dismal. Areas covered: A wealth of research over the past decade has revolutionized our understanding of the molecular basis of DMG, revealing potential targetable vulnerabilities for treatment of this lethal childhood cancer. However, obstacles to successful clinical implementation of novel therapies remain, including effective delivery across the blood–brain barrier (BBB) to the tumor site. Here, we review relevant literature and clinical trials and discuss direct drug delivery via convection-enhanced delivery (CED) as a promising treatment modality for DMG. We outline a comprehensive molecular, pharmacological, and procedural approach that may offer hope for afflicted patients and their families. Expert opinion: Challenges remain in successful drug delivery to DMG. While CED and other techniques offer a chance to bypass the BBB, the variables influencing successful intratumoral targeting are numerous and complex. We discuss these variables and potential solutions that could lead to the successful clinical implementation of preclinically promising therapeutic agents.
AB - Introduction: Despite much progress, the prognosis for H3K27-altered diffuse midline glioma (DMG), previously known as diffuse intrinsic pontine glioma when located in the brainstem, remains dark and dismal. Areas covered: A wealth of research over the past decade has revolutionized our understanding of the molecular basis of DMG, revealing potential targetable vulnerabilities for treatment of this lethal childhood cancer. However, obstacles to successful clinical implementation of novel therapies remain, including effective delivery across the blood–brain barrier (BBB) to the tumor site. Here, we review relevant literature and clinical trials and discuss direct drug delivery via convection-enhanced delivery (CED) as a promising treatment modality for DMG. We outline a comprehensive molecular, pharmacological, and procedural approach that may offer hope for afflicted patients and their families. Expert opinion: Challenges remain in successful drug delivery to DMG. While CED and other techniques offer a chance to bypass the BBB, the variables influencing successful intratumoral targeting are numerous and complex. We discuss these variables and potential solutions that could lead to the successful clinical implementation of preclinically promising therapeutic agents.
KW - Diffuse midline glioma
KW - H3 K27-altered
KW - H3 K27M
KW - blood–brain barrier
KW - convection-enhanced delivery
KW - diffuse intrinsic pontine glioma
KW - pharmacokinetics
KW - targeted therapeutics
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U2 - 10.1080/14728222.2023.2177531
DO - 10.1080/14728222.2023.2177531
M3 - Article
C2 - 36744399
AN - SCOPUS:85148052498
SN - 1472-8222
VL - 27
SP - 9
EP - 17
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 1
ER -