Related Experiment Video
Updated: May 22, 2026
07:40
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
Targeting synthetic lethal interactions between Myc and the eIF4F complex impedes tumorigenesis
Chen-Ju Lin1, Zeina Nasr, Prem K Premsrirut
1Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Cell Reports
|May 11, 2012
Summary
Targeting eukaryotic initiation factor 4F (eIF4F) shows promise in cancer therapy. Inhibiting eIF4F is synthetically lethal with elevated Myc, a key driver in lymphoma development, offering a tumor-specific vulnerability.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Translation regulation by mTOR controls eukaryotic initiation factor 4F (eIF4F) complex assembly.
- Dysregulated eIF4F activity is implicated in oncogenesis and chemotherapy resistance.
- eIF4F is a potential therapeutic target for antineoplastic strategies.
Purpose of the Study:
- To investigate the role of endogenous eIF4F in Myc-driven tumor initiation.
- To define eIF4F as a critical client of Myc in cancer development.
- To explore the therapeutic potential of targeting eIF4F in Myc-dependent tumors.
Main Methods:
- Utilized a novel inducible RNAi platform for gene manipulation.
- Employed pharmacological agents to target eIF4F activity.
- Studied the Emicro-Myc lymphoma model at prelymphomatous and premalignant stages.
Main Results:
- Elevated Myc levels correlated with deregulated eIF4F activity in premalignant lymphoma cells.
- Inhibition of eIF4F demonstrated synthetic lethality with high Myc levels.
- Suppression of eIF4F reduced cycling premalignant B cells and delayed tumor onset.
- Organismal eIF4F suppression was tolerated in normal regenerating cells and reversible.
Conclusions:
- Endogenous eIF4F plays a critical role in Myc-dependent tumor initiation.
- eIF4F represents a tumor-specific vulnerability exploitable for cancer therapy.
- Targeting eIF4F offers a promising therapeutic strategy for Myc-driven cancers.
Related Concept Videos
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:06Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...
02:57Targeted 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...
There are several types of targeted therapies against specific...
02:38Mitogens 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...
01:52Eukaryotic Transcription Inhibitors
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
02:50Combination 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...
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...