Related Experiment Video

Updated: Mar 19, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

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

Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate

Hsian-Yu Wang1, Min-Kung Hsu2, Kai-Hsuan Wang3

  • 1Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes (NHRI), Zhunan, Miaoli County, Republic of China; Institute of Molecular Medicine and Bioengineering, National Chiao Tung University (NCTU), Hsinchu, Taiwan, Republic of China.

Oncotargets and Therapy
|June 11, 2016
PubMed
Abstract

Insights

Non-small cell lung cancer cells use immediate adhesion responses to resist EGFR TKIs. Combining EGFR inhibitors with Src family inhibitors like dasatinib enhances cancer cell killing by blocking this survival pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective against non-small cell lung cancer (NSCLC) with sensitive mutations.
  • Drug resistance limits TKI efficacy, necessitating new therapeutic strategies.
  • Immediate cellular responses to TKIs, rather than long-term adaptation, are often overlooked in resistance studies.

Purpose of the Study:

  • To investigate the immediate cellular responses of NSCLC cells upon treatment with EGFR TKIs.
  • To identify mechanisms by which NSCLC cells counteract EGFR-targeted therapy in the short term.

Main Methods:

  • Gene expression and pathway analysis of EGFR TKI-treated NSCLC cells (PC9 and H1975).
  • Functional validation using small-hairpin RNAs and small-molecule inhibitors targeting identified pathways.
  • Combination therapy studies involving EGFR TKIs and Src family inhibitors (dasatinib).

Main Results:

  • NSCLC cells exhibit enhanced adhesion-related responses as an immediate, apoptosis-countering mechanism upon EGFR TKI exposure.
  • Adhesion pathways are significantly enriched in gefitinib-treated PC9 cells.
  • Dasatinib, a Src family inhibitor, effectively inhibits cell adhesion and potentiates the cytotoxic effects of EGFR TKIs, preventing TKI-induced apoptosis escape.

Conclusions:

  • NSCLC cells utilize adhesion responses as an immediate survival pathway to resist EGFR-targeted therapy.
  • Simultaneous targeting of EGFR signaling and adhesion pathways holds promise for enhancing TKI efficacy in NSCLC treatment.
Keywords:
adhesion responsecell stress responsedrug resistancegene set enrichment analysis

More Related Videos

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.5K
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

Related Concept Videos

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
Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
4.7K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.8K
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
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.8K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
20.4K