Related Experiment Video

Updated: Sep 28, 2025

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

8.9K

Role of immunotherapy in metastatic EGFRm NSCLC: Is it relevant?

Boman Dhabhar1, Tarini P Sahoo2, J K Akshay3

  • 1Department of Medical Oncology, Fortis Hospital, Mulund, Mumbai, Maharashtra, India.

Indian Journal of Cancer
|March 28, 2022
PubMed

Insights

Treatment resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is common in metastatic non-small cell lung cancer (NSCLC). Combination therapies involving immune checkpoint inhibitors (ICIs) show promise for TKI-resistant EGFR-mutant NSCLC.

Area of Science:

  • Oncology
  • Pharmacology
  • Immunotherapy

Background:

  • Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have improved outcomes for metastatic non-small cell lung cancer (NSCLC) with EGFR mutations (EGFRm).
  • Acquired resistance to EGFR-TKIs, including third-generation Osimertinib, remains a significant challenge, limiting treatment options for patients with EGFRm NSCLC.
  • Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) pathway were investigated for EGFRm NSCLC, but initial clinical results did not demonstrate a survival benefit due to factors like low tumor mutational burden and alternative immune escape mechanisms.

Purpose of the Study:

  • To explore therapeutic strategies for TKI-resistant metastatic EGFRm NSCLC.
  • To review the clinical data on ICI use in metastatic EGFRm NSCLC.
  • To discuss the emerging role of combination regimens involving EGFR-TKIs and ICIs in this patient population.

Main Methods:

  • Review of preclinical studies and clinical trial data regarding EGFR-TKI resistance in NSCLC.
  • Analysis of the efficacy and limitations of immune checkpoint inhibitors (ICIs) in EGFRm NSCLC.
  • Exploration of emerging combination strategies combining EGFR-TKIs with ICIs.

Main Results:

  • Preclinical studies suggested increased PD-L1 expression with EGFR-TKIs, but clinical trials showed no survival benefit for ICIs in EGFRm NSCLC.
  • Factors contributing to ICI failure include low tumor mutational burden, reduced PD-L1 expression, and alternative immune evasion strategies.
  • A subgroup analysis of the IMpower150 study indicated a potential survival benefit with atezolizumab plus chemotherapy in TKI-pre-treated EGFRm patients, prompting further investigation into combination therapies.

Conclusions:

  • Current NCCN guidelines do not recommend immunotherapy for metastatic EGFRm NSCLC due to limited efficacy.
  • Combination regimens of EGFR-TKIs and ICIs are under investigation and may offer improved response rates and durable disease control for TKI-refractory EGFRm NSCLC.
  • Further research is crucial to elucidate the molecular and cellular mechanisms underlying the clinical benefits of these combination strategies.
Keywords:
Epidermal growth factor receptorsimmune checkpoint inhibitorsnon-small cell lung cancerprogramed cell death-1programmed cell death ligand-1tyrosine kinase inhibitors

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

8.0K
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer07:59

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

1.3K

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...
7.0K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
693
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...
7.9K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.8K