Related Experiment Video

Updated: May 23, 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

MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition

Dai Horiuchi1, Leonard Kusdra, Noelle E Huskey

  • 1Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

The Journal of Experimental Medicine
|March 21, 2012
PubMed

Insights

Triple-negative breast cancers show high MYC pathway activity, driving poor prognosis. Targeting this with cyclin-dependent kinase (CDK) inhibitors induces tumor regression, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) lacks targeted therapies and presents a clinical challenge.
  • Elevated MYC expression and pathway activity are characteristic of TNBC.
  • MYC signaling correlates with poor prognosis in primary breast tumors.

Purpose of the Study:

  • To investigate the role of MYC in TNBC.
  • To explore therapeutic strategies targeting MYC-driven TNBC.
  • To evaluate the efficacy of cyclin-dependent kinase (CDK) inhibitors in TNBC.

Main Methods:

  • Analysis of MYC expression and regulatory genes in TNBC.
  • Assessment of MYC signaling in relation to chemotherapy response and prognosis.
  • Utilizing a synthetic-lethal approach with CDK inhibition in TNBC xenografts.
  • Investigating the role of BIM in CDK inhibitor-induced apoptosis.

Main Results:

  • TNBC tumors exhibit significantly elevated MYC expression and pathway activity.
  • MYC signaling did not predict chemotherapy response but was linked to poor prognosis.
  • CDK inhibition led to substantial tumor regression in TNBC xenografts.
  • Upregulation of BIM by CDK inhibition contributes to the synthetic-lethal effect.

Conclusions:

  • Elevated MYC is a key vulnerability in TNBC.
  • CDK inhibitors represent a promising synthetic-lethal strategy for MYC-driven TNBC.
  • Targeting MYC with CDK inhibitors offers a novel therapeutic avenue for aggressive breast cancers.

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

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Related Concept Videos

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...
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...
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...
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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...