Related Experiment Video

Updated: Jun 25, 2025

Inducible and Reversible Dominant-negative DN Protein Inhibition
08:35

Inducible and Reversible Dominant-negative DN Protein Inhibition

Published on: January 7, 2019

8.4K

A synthetic lethal dependency on casein kinase 2 in response to replication-perturbing therapeutics in RB1-deficient

Daria Bulanova1,2, Yevhen Akimov2, Wojciech Senkowski1

  • 1Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.

Science Advances
|May 23, 2024
PubMed

Insights

Loss of RB1 in ovarian and breast cancers creates a vulnerability to CK2 inhibition, offering a new therapeutic strategy. Targeting CK2 may overcome resistance to standard treatments like carboplatin and PARP inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • High-grade serous ovarian carcinoma (HGSC) and triple-negative breast cancer (TNBC) frequently develop therapy resistance.
  • Identifying predictive biomarkers and novel therapeutic combinations is crucial for improving patient outcomes.

Purpose of the Study:

  • To identify synthetic lethal dependencies in RB1-deficient cancer cells.
  • To evaluate casein kinase 2 (CK2) inhibition as a therapeutic strategy against HGSC and TNBC.

Main Methods:

  • CRISPR knockout screens were employed to identify genetic dependencies.
  • RB1-deficient cell lines and patient-derived organoids were treated with CK2 inhibitors.
  • Cell cycle progression, DNA damage, and cell death were analyzed.

Main Results:

  • Loss of RB1 confers a synthetic lethal dependency on CK2 in cells treated with replication-perturbing agents.
  • CK2 inhibition in RB1-deficient cells leads to p130 degradation, S phase accumulation, and aneuploidy.
  • CK2 inhibition demonstrated efficacy in patient-derived HGSC organoids, preventing regrowth after carboplatin or niraparib treatment.

Conclusions:

  • CK2 inhibition represents a promising therapeutic approach for RB1-deficient HGSC and TNBC.
  • This strategy could overcome resistance to standard therapies in a significant proportion of patients with these cancers.

More Related Videos

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.3K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

17.9K

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.2K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.3K
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...
3.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
3.9K