Related Experiment Video

Updated: May 12, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

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

Signaling cross-talk in the resistance to HER family receptor targeted therapy

H Yamaguchi1, S-S Chang2, J L Hsu3

  • 1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Oncogene
|April 2, 2013
PubMed

Insights

Targeting cancer growth pathways like epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) is effective, but drug resistance emerges. Understanding signaling cross-talk is key to overcoming this resistance and improving cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) are crucial in cancer initiation and progression.
  • Targeted therapies inhibiting EGFR/HER2 are vital in cancer treatment but face significant drug resistance.
  • Molecular mechanisms, particularly signaling cross-talk, underlie both intrinsic and acquired resistance to these therapies.

Purpose of the Study:

  • To review signaling cross-talk mechanisms contributing to resistance against EGFR/HER2 inhibitors.
  • To explore cross-talk at receptor, mediator, and effector levels.
  • To discuss strategies for overcoming resistance by targeting these cross-talk pathways.

Main Methods:

  • Literature review focusing on molecular mechanisms of resistance to EGFR/HER2 inhibitors.
  • Analysis of signaling cross-talk at various molecular levels.
  • Identification of potential therapeutic strategies targeting cross-talk pathways.

Main Results:

  • Signaling cross-talk between EGFR/HER2 and other pathways is a major driver of drug resistance.
  • Cross-talk occurs at receptor, mediator, and effector levels, involving pathways like Notch, Wnt, and TNFR/IKK/NF-κB.
  • These cross-talk networks represent potential targets for resensitizing cancer cells to EGFR/HER2 inhibitors.

Conclusions:

  • Understanding signaling cross-talk is essential for developing strategies to overcome resistance to EGFR/HER2 targeted therapies.
  • Targeting cross-talk pathways, including those involving Notch, Wnt, and TNFR/IKK/NF-κB, offers a promising approach to enhance drug efficacy.
  • Further research into these complex signaling networks can lead to improved cancer treatment outcomes.

More Related Videos

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes08:32

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

Published on: May 23, 2025

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function08:04

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

Related Concept Videos

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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...