Related Experiment Video

Updated: Jun 19, 2026

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

Development of 'synthetic lethal' strategies to target BRCA1-deficient breast cancer

Max S Wicha

    Breast Cancer Research : BCR
    |October 7, 2009
    PubMed

    Insights

    BRCA1-deficient breast cancer cells show selective sensitivity to EZH2 inhibitors, supporting the synthetic lethal approach. This preclinical finding suggests polycomb gene inhibitors could be a novel targeted therapy for these tumors.

    Area of Science:

    • Oncology
    • Genetics
    • Molecular Biology

    Background:

    • The 'synthetic lethal' concept in cancer therapeutics posits that specific genetic defects in cancer cells can be targeted for selective killing.
    • Poly(ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in BRCA1-deficient breast cancers, validating this concept.
    • BRCA1 deficiency is a key molecular alteration in certain breast cancers, impacting DNA repair pathways.

    Discussion:

    • A new study demonstrates that BRCA1-deficient mouse mammary tumor cells exhibit selective sensitivity to inhibitors targeting the polycomb gene EZH2.
    • This finding provides preclinical validation for targeting EZH2 as a synthetic lethal strategy in BRCA1-deficient cancers.
    • EZH2 is a component of the Polycomb Repressive Complex 2 (PRC2), involved in epigenetic gene silencing.

    Key Insights:

    • BRCA1-deficient cells are selectively vulnerable to EZH2 inhibition.
    • Targeting EZH2 represents a potential novel therapeutic strategy for BRCA1-mutated breast cancers.
    • This research reinforces the utility of synthetic lethality in developing targeted cancer treatments.

    Outlook:

    • Further investigation into polycomb gene inhibitors, specifically EZH2 inhibitors, is warranted for clinical development.
    • These inhibitors could offer a new avenue for treating patients with BRCA1-deficient breast tumors.
    • The study opens possibilities for exploring synthetic lethal interactions with other epigenetic regulators in cancer therapy.

    More Related Videos

    Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells07:23

    Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

    Published on: May 30, 2025

    Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

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

    Published on: August 12, 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...
    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...
    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...
    In-vitro Mutagenesis01:16

    In-vitro Mutagenesis

    To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
    The Intrinsic Apoptotic Pathway01:31

    The Intrinsic Apoptotic Pathway

    Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...