Related Experiment Video

Updated: May 28, 2025

Identification of Kinase-substrate Pairs Using High Throughput Screening
11:13

Identification of Kinase-substrate Pairs Using High Throughput Screening

Published on: August 29, 2015

8.1K

High-throughput screening identifies Aurora kinase B as a critical therapeutic target for Merkel cell carcinoma

Tara Gelb1, Khalid A Garman1, Daniel Urban2

  • 1Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Nature Communications
|February 12, 2025
PubMed

Insights

Researchers screened compounds to find new Merkel cell carcinoma (MCC) treatments. Aurora kinase B (AURKB) inhibitors, like AZD2811, show promise, particularly for virus-positive MCC, reducing tumor growth in mice.

Area of Science:

  • Oncology
  • Dermatology
  • Virology

Background:

  • Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer.
  • Most MCC cases are linked to Merkel cell polyomavirus (VP-MCC), while others are virus-negative (VN-MCC).
  • Current treatments like immune checkpoint inhibitors have limited durable response rates in metastatic MCC.

Purpose of the Study:

  • To identify novel therapeutic targets and treatments for both VP-MCC and VN-MCC.
  • To investigate the distinct response profiles of VP-MCC and VN-MCC to compound screening.
  • To evaluate the efficacy of Aurora kinase inhibitors, specifically targeting AURKB, in MCC treatment.

Main Methods:

  • Screened approximately 4,000 compounds for MCC cell viability reduction.
  • Utilized RNA interference (RNAi) screening to identify essential genes for MCC survival.
  • Tested the selective Aurora B kinase (AURKB) inhibitor AZD2811 and its nanoparticle formulation (AZD2811NP) in MCC cell lines and mouse xenograft models.

Main Results:

  • VP-MCC and VN-MCC demonstrated distinct responses to compound screening.
  • Aurora kinase inhibitors selectively reduced VP-MCC viability.
  • RNAi screening identified AURKB as crucial for MCC survival, especially in VP-MCC.
  • AZD2811 induced mitotic disruption and apoptosis in MCC cells, with higher efficacy in VP-MCC.
  • AZD2811NP significantly inhibited tumor growth and improved survival in both VP-MCC and VN-MCC mouse models.

Conclusions:

  • AURKB is a promising therapeutic target for Merkel cell carcinoma.
  • AZD2811 nanoparticles represent a potential treatment strategy for both virus-positive and virus-negative MCC.
  • Unbiased compound and RNAi screening effectively identified novel therapeutic avenues for aggressive skin cancers.

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

14.8K
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

7.8K

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...
7.4K
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...
6.4K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
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
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...
4.8K