Related Experiment Video

Updated: Mar 13, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

7.3K

Blocking NOTCH pathway can enhance the effect of EGFR inhibitor through targeting CD133+ endometrial cancer cells

Chao Shang1, Bin Lang2, Li-Rong Meng2

  • 1a Department of Neurobiology , China Medical University , Shenyang , P. R. China.

Cancer Biology & Therapy
|October 30, 2016
PubMed

Insights

Targeting NOTCH pathway in CD133+ cancer stem cells enhances EGFR inhibition efficacy for endometrial cancer treatment. This combination therapy overcomes drug resistance, offering a novel strategy for this disease.

Area of Science:

  • Gynecologic Oncology
  • Cancer Stem Cell Biology
  • Molecular Therapeutics

Background:

  • Endometrial cancer drug resistance is a major challenge, often linked to cancer stem cells (CSCs).
  • CD133-positive cells are identified as CSCs in endometrial cancer, with the NOTCH pathway crucial for their self-renewal and chemoresistance.
  • Existing therapies targeting biomarkers like EGFR show promise but are limited by CSC-mediated resistance.

Purpose of the Study:

  • To develop a therapeutic strategy combining NOTCH pathway inhibition with EGFR inhibition to overcome drug resistance in endometrial cancer.
  • To investigate the role of CD133+ cells and NOTCH pathway activation in endometrial cancer stemness and chemoresistance.

Main Methods:

  • Isolation and characterization of CD133+ and CD133- cells from Ishikawa endometrial cancer cell line.
  • Assessment of NOTCH pathway activation, proliferation, and apoptosis rates in CD133+ versus CD133- cells.
  • Nude mouse xenograft experiments to evaluate tumor-initiating capacity.
  • In vitro combination therapy studies using NOTCH inhibitor (DAPT) and EGFR inhibitor (AG1478) on endometrial cancer cell lines.

Main Results:

  • CD133+ cells exhibited higher proliferation and lower apoptosis rates, confirming their CSC properties.
  • CD133+ cells demonstrated superior tumor-initiating capacity in vivo.
  • Combination therapy with DAPT and AG1478 showed improved efficacy compared to monotherapies in endometrial cancer cell lines.

Conclusions:

  • NOTCH pathway activation is critical for maintaining CD133+ cancer stem cells in endometrial cancer.
  • Targeting the NOTCH pathway in CD133+ cells, in conjunction with EGFR inhibition, represents a promising therapeutic strategy.
  • This combined approach offers a novel avenue for overcoming drug resistance and improving treatment outcomes in endometrial cancer.
Keywords:
Cancer stem cellEGFRNOTCHendometrial cancer

More Related Videos

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.7K
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.3K

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.8K
Mitogens and the Cell Cycle02:38

Mitogens 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...
8.3K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.6K
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...
6.1K
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...
9.1K