Related Experiment Video

Updated: Apr 23, 2026

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
06:29

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

3.4K

Aurora kinases as targets in drug-resistant neuroblastoma cells

Martin Michaelis1, Florian Selt2, Florian Rothweiler2

  • 1Institut für Medizinische Virologie, Klinikum der Goethe-Universität, Frankfurt am Main, Germany; Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury, United Kingdom.

Plos One
|October 1, 2014
PubMed

Insights

Aurora kinase inhibitors like tozasertib and alisertib show promise against neuroblastoma, particularly in drug-resistant and p53 wild-type cases. These inhibitors target key cell signaling pathways, offering new therapeutic avenues for difficult-to-treat neuroblastoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Neuroblastoma is a pediatric cancer with limited treatment options for refractory cases.
  • Aurora kinases are crucial for cell division and are implicated in cancer progression.
  • Acquired drug resistance remains a significant challenge in neuroblastoma treatment.

Purpose of the Study:

  • To evaluate the efficacy of tozasertib and alisertib in neuroblastoma cell lines with acquired drug resistance.
  • To elucidate the mechanisms of action of these aurora kinase inhibitors.
  • To explore potential combination therapies for enhanced anti-neuroblastoma effects.

Main Methods:

  • Testing tozasertib and alisertib on a panel of neuroblastoma cell lines.
  • Assessing drug sensitivity in the nanomolar range.
  • Analyzing effects on aurora kinase signaling, cell cycle, apoptosis, and p53 response.
  • Investigating the role of ABCB1 expression and combination with nutlin-3.

Main Results:

  • Both tozasertib and alisertib demonstrated significant anti-neuroblastoma activity.
  • Inhibition of aurora kinase signaling, G2/M cell cycle arrest, and apoptosis were observed.
  • ABCB1 expression influenced alisertib's activity, but not tozasertib's.
  • Combination with nutlin-3 enhanced inhibitor activity in p53 wild-type cells.

Conclusions:

  • Aurora kinases represent viable therapeutic targets for therapy-refractory neuroblastoma.
  • The findings support further investigation of aurora kinase inhibitors, especially in p53 wild-type neuroblastoma.
  • Combination strategies, including with MDM2 inhibitors, may overcome resistance mechanisms.

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

14.5K
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.5K

Related Concept Videos

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...
6.9K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
64.5K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
2.6K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
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...
3.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.3K