Related Experiment Video

Updated: Jan 30, 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

9.2K

Treatment options and considerations for acquired resistance in EGFR mutation-positive non-small-cell lung cancer

X Le1, S Popat2, J V Heymach1

  • 1Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.

ESMO Open
|January 28, 2026
PubMed

Insights

New treatments are emerging for EGFR-mutation positive non-small-cell lung cancer (NSCLC) that has become resistant to tyrosine kinase inhibitors (TKIs). Repeat biopsies and personalized therapies are key to overcoming resistance and improving patient outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-mutation positive (EGFRm-positive) advanced non-small-cell lung cancer (NSCLC).
  • Acquired resistance to EGFR TKIs is a significant challenge, and optimal subsequent treatment strategies are not well-established.

Purpose of the Study:

  • To review the latest clinical trial data on treatment approaches for overcoming acquired resistance to EGFR TKIs in EGFRm-positive advanced NSCLC.
  • To summarize potential strategies including repeat biopsies, identification of resistance mutations, and novel combination therapies.

Main Methods:

  • Review of recent clinical trial data and literature on acquired resistance to EGFR TKIs in NSCLC.
  • Analysis of treatment outcomes for various strategies, including chemotherapy, targeted therapies, and novel combinations.
  • Consideration of factors such as histological transformation and brain metastases.

Main Results:

  • Repeat biopsy is crucial for detecting histological transformation, for which platinum-based chemotherapy is the standard.
  • While identifying actionable resistance mutations can inform personalized treatment, it is not yet a clear standard of care.
  • Combinations with immunotherapy, bispecific antibodies, and antibody-drug conjugates show promise in improving progression-free survival and overall survival, including in patients with brain metastases.

Conclusions:

  • Effective management of acquired resistance to EGFR TKIs in NSCLC requires a multi-faceted approach.
  • Repeat biopsies and consideration of novel combination therapies are essential for improving outcomes.
  • Shared decision-making between physicians and patients is increasingly important given the expanding treatment options and their associated side effects.
Keywords:
EGFR mutationacquired resistancenon-small-cell lung cancer

More Related Videos

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

408
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

9.3K

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...
3.8K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.9K
Mutations01:39

Mutations

Overview
94.5K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.5K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.9K
Design Consideration01:22

Design Consideration

Designing a structure involves a series of considerations, primarily the material's ultimate strength, calculated through tests that measure changes under increased force until the material reaches its breaking point or limit. The ultimate load, where the material breaks, is divided by its original cross-sectional area, resulting in the ultimate normal stress or strength. The ultimate shearing stress is another significant factor taken into account.
The factor of safety is another key...
571