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Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

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In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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Correction: Phase I/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors.

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Visual morbidity, long-term outcome and prognostic factors in infants and young children with optic pathway low-grade glioma.

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Tempered Optimism: Advances in the Precision Medicine Era for Pediatric Low-Grade Glioma.

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Related Experiment Video

Updated: May 1, 2026

A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
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RAS/MAPK inhibition in pediatric gliomas.

Anfal Jasem M Alshammari1, Darren Hargrave2, Anirban Das1

  • 1Department of Paediatrics, University of Toronto and Hospital for Sick Children, Toronto, Canada.

Neuro-Oncology Advances
|April 30, 2026
PubMed
Summary
This summary is machine-generated.

Targeted therapies, specifically RAS/MAPK pathway inhibitors, offer a new treatment era for pediatric low-grade glioma. These oral medications show improved response rates compared to chemotherapy, though challenges remain.

Keywords:
BRAF inhibitionMEK inhibitionhigh-grade gliomalow-grade gliomatargeted therapy

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Area of Science:

  • Neuro-oncology
  • Pediatric oncology
  • Molecular targeted therapy

Background:

  • Pediatric low-grade glioma is a chronic disease with significant morbidity.
  • Chemotherapy has been the historical standard, often requiring multiple treatment lines for recurrent disease.
  • The RAS/MAPK pathway is frequently altered in these gliomas.

Purpose of the Study:

  • To review the current landscape of RAS/MAPK inhibitor use in pediatric gliomas.
  • To summarize completed and ongoing clinical trials of these targeted therapies.
  • To highlight challenges and future research directions in this field.

Main Methods:

  • Review of completed and ongoing clinical trials.
  • Analysis of approved RAS/MAPK inhibitors for specific indications.
  • Discussion of toxicities, treatment duration, response durability, and resistance mechanisms.

Main Results:

  • RAS/MAPK inhibitors represent a new treatment paradigm with improved response rates over chemotherapy.
  • Several drugs targeting this pathway have received approval for specific pediatric glioma indications.
  • Ongoing trials are exploring upfront use, combination therapies, and novel agents.

Conclusions:

  • RAS/MAPK inhibitors have transformed pediatric glioma management.
  • Key challenges include managing unique toxicities and understanding treatment duration, response durability, and resistance.
  • Future research should focus on optimizing therapy and addressing long-term impacts for patients.