Related Experiment Video

Updated: May 21, 2025

Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice
05:10

Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice

Published on: October 3, 2010

12.1K

Targeting processive transcription for Myc-driven circuitry in medulloblastoma

Lays Martin Sobral1, Faye M Walker1, Krishna Madhavan1

  • 1Morgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.

Neuro-Oncology
|May 15, 2025
PubMed
Abstract

Insights

Targeting CDK9, a dependency in Myc-amplified medulloblastoma (Myc-MB), shows promise. Inhibiting CDK9 and CDK7 disrupts tumor growth programs, offering a new therapeutic strategy for high-risk childhood brain tumors.

Area of Science:

  • Pediatric oncology
  • Molecular biology
  • Cancer genetics

Background:

  • Medulloblastoma is the most common malignant pediatric brain tumor.
  • Myc-amplified medulloblastoma (Myc-MB) has poor outcomes despite treatment.
  • Myc drives pro-survival pathways, but direct targeting is difficult.

Purpose of the Study:

  • Identify therapeutic vulnerabilities in Myc-MB.
  • Investigate CDK9 as a potential drug target.
  • Evaluate CDK9/7 inhibitors for Myc-MB treatment.

Main Methods:

  • CRISPR-Cas9 screens to find Myc-MB dependencies.
  • Chromatin conformation capture (Hi-C) to map enhancer-promoter interactions.
  • In vitro and xenograft models treated with CDK9/7 inhibitors.

Main Results:

  • CDK9 identified as a conserved dependency in Myc-MB across multiple screens.
  • CDK9 inhibition is effective and synergistic with CDK7 inhibition.
  • Inhibiting CDK9/7 disrupts enhancer-promoter activity and downregulates Myc programs, reducing tumor growth.

Conclusions:

  • CDK9 inhibition is a promising therapeutic strategy for Myc-MB.
  • Targeting transcriptional CDKs offers an indirect approach to drugging Myc-driven circuitry.
  • This study provides a rationale for clinical investigation of CDK9 inhibitors in Myc-MB.
Keywords:
CDK7CDK9Mycmedulloblastoma

More Related Videos

Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma10:58

Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma

Published on: February 22, 2015

12.9K
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy09:40

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy

Published on: October 4, 2019

5.6K

Related Concept Videos

Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
3.9K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.8K
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Transcription Initiation01:47

Transcription Initiation

Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
16.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K