Related Experiment Video

Updated: Mar 24, 2026

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
09:38

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

Addressing epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer

Shoko Noda1, Shintaro Kanda1

  • 1a Department of Thoracic Oncology , National Cancer Center Hospital , Tokyo , Japan.

Expert Review of Respiratory Medicine
|March 10, 2016
PubMed

Insights

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improve survival in advanced non-small cell lung cancer (NSCLC). This review covers strategies to overcome acquired resistance to EGFR-TKIs, a major clinical challenge.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have advanced treatment for EGFR-mutant non-small cell lung cancer (NSCLC).
  • Acquired resistance to EGFR-TKIs is a significant clinical challenge, leading to tumor progression.
  • Understanding resistance mechanisms is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To review current strategies for preventing and overcoming acquired resistance to EGFR-TKIs in NSCLC.
  • To highlight the role of T790M mutations in resistance and the development of third-generation EGFR-TKIs.
  • To explore combination therapies, including cytotoxic chemotherapy, as a means to enhance EGFR-TKI efficacy.

Main Methods:

  • Literature review of studies on EGFR-TKI resistance mechanisms in NSCLC.
  • Analysis of clinical data on third-generation EGFR-TKIs (e.g., osimertinib).
  • Evaluation of preclinical and clinical evidence for combination treatment approaches.

Main Results:

  • T790M mutation is a primary mechanism of acquired resistance to first- and second-generation EGFR-TKIs.
  • Third-generation EGFR-TKIs demonstrate efficacy against T790M-positive NSCLC.
  • Combination therapies, particularly with chemotherapy, show promise in overcoming resistance and prolonging survival.

Conclusions:

  • Acquired resistance to EGFR-TKIs remains a critical issue in NSCLC management.
  • Targeting T790M mutations with newer agents and employing combination strategies are key to improving patient outcomes.
  • Continued research into novel therapeutic approaches is essential for durable responses in EGFR-mutant NSCLC.
Keywords:
Non-small cell lung cancerT790M mutationchemotherapyepidermal growth factor receptor mutationepidermal growth factor receptor tyrosine kinase inhibitor

More Related Videos

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
A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

10.7K

Related Concept Videos

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...
3.9K
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...
8.4K
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
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

1.5K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
633
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...
66