Related Experiment Video

Updated: Jun 20, 2026

Nanoparticle Delivery of an Oligonucleotide Payload in a Glioblastoma Multiforme Animal Model
09:02

Nanoparticle Delivery of an Oligonucleotide Payload in a Glioblastoma Multiforme Animal Model

Published on: September 27, 2024

Disrupting polyamine homeostasis as a therapeutic strategy for neuroblastoma

Nicholas F Evageliou1, Michael D Hogarty

  • 1Division of Oncology, The Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 1, 2009
PubMed

Insights

MYC gene deregulation drives cancer by boosting polyamine production. Inhibiting polyamine synthesis, particularly in neuroblastoma, shows promise for cancer treatment and synergizes with chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MYC network deregulation is implicated in numerous human cancers, influencing over 15% of the genome.
  • MYC is crucial for cellular bioenergetics and biomass, with polyamines being essential for these functions.
  • Enhanced polyamine biosynthesis is linked to cancer progression, and its inhibition may impede malignant transformation.

Purpose of the Study:

  • To review the role of MYC in regulating polyamine biosynthesis in cancer.
  • To explore the therapeutic potential of polyamine depletion agents in MYC-driven cancers, including neuroblastoma.

Main Methods:

  • Review of existing literature on MYC, polyamine metabolism, and cancer.
  • Analysis of studies involving polyamine synthesis inhibitors like DFMO and SAM486 in preclinical cancer models.
  • Examination of the impact of MYC activation on polyamine pathway enzymes.

Main Results:

  • ODC, the rate-limiting enzyme in polyamine biosynthesis, is a direct MYC target.
  • Repressing polyamine production can attenuate MYC's role in tumor initiation and progression.
  • Selective inhibition of polyamine enzymes reduces tumorigenesis and enhances chemotherapy efficacy in preclinical models, notably in neuroblastoma.

Conclusions:

  • Targeting polyamine biosynthesis represents a promising therapeutic strategy for MYC-driven cancers.
  • Polyamine depletion agents show potential for clinical application in neuroblastoma and other advanced cancers where MYC is operative.
  • Further investigation into polyamine depletion agents could lead to novel cancer treatment regimens.

Related Concept Videos

Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists01:29

Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates these...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Drugs Affecting Neurotransmitter Release or Uptake01:21

Drugs Affecting Neurotransmitter Release or Uptake

Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...