Related Experiment Video

Updated: Jun 26, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer

N McCabe1, M A Cerone, T Ohishi

  • 1Cancer Research UK Gene Function and Regulation Group, Institute of Cancer Research, London, UK.

Oncogene
|February 3, 2009
PubMed

Insights

Inhibiting Tankyrase 1 selectively kills cancer cells with BRCA1 or BRCA2 mutations. This approach targets genome instability and centrosome amplification in BRCA-associated cancers.

Area of Science:

  • Genetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • BRCA1 and BRCA2 proteins are crucial for maintaining genome stability.
  • Loss-of-function mutations in BRCA1/BRCA2 increase susceptibility to breast and other cancers.
  • Targeting DNA maintenance pathways offers a therapeutic strategy for BRCA-deficient tumors.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting Tankyrase 1 in BRCA-deficient cancers.
  • To explore the link between Tankyrase 1 inhibition and BRCA deficiency phenotypes.

Main Methods:

  • Utilized cell-based assays to assess the effects of Tankyrase 1 inhibition.
  • Examined the impact of Tankyrase 1 inhibition on BRCA-deficient cells.
  • Analyzed centrosome amplification as a phenotype associated with BRCA deficiency.

Main Results:

  • Inhibition of Tankyrase 1 demonstrated selective lethality in BRCA-deficient cells.
  • Tankyrase 1 inhibition exacerbated the centrosome amplification phenotype in BRCA-deficient cells.
  • This selectivity suggests a novel therapeutic vulnerability.

Conclusions:

  • Tankyrase 1 inhibition is selectively lethal to cells with BRCA1/BRCA2 mutations.
  • Targeting Tankyrase 1 may represent a viable therapeutic strategy for BRCA-associated cancers.
  • The findings provide a basis for developing new treatments for these specific cancer types.

More Related Videos

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

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 specific...
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...
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...
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...
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...
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...