Related Experiment Video
Updated: Jul 22, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Emerging agents for the treatment of advanced or metastatic NSCLC without actionable genomic alterations with
Ticiana Leal1, Mark A Socinski2
1Emory University Winship Cancer Institute, USA.
Introduction:
Lung cancer is the second most common cancer in the world and the leading cause of cancer-related mortality. Immune checkpoint inhibitors (ICIs), as monotherapy or in combination with platinum-based chemotherapy, have emerged as the standard of care first-line treatment option for patients with advanced non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGAs). Despite significant improvements in patient outcomes with these regimens, primary or acquired resistance is common and most patients develop disease progression, resulting in poor survival.
Areas Covered:
We review the current treatments commonly used for NSCLC without AGAs in the first-line and subsequent settings and describe the unmet needs for these patients in the second-line setting, including a lack of standard definitions for primary and required resistance, and few effective treatment options for patients who develop progression of their disease on first-line therapy. We describe key mechanisms of resistance to ICIs and emerging therapies that are being investigated for patients who develop progression on ICIs and platinum-based chemotherapy.
Expert Opinion:
Emerging agents in development have a variety of different mechanisms of action and will likely change standard of care for second-line therapy and beyond for patients with NSCLC without AGAs in the future.
Insights
Immune checkpoint inhibitors improve outcomes for advanced non-small cell lung cancer (NSCLC) without actionable genomic alterations. However, resistance is common, highlighting the need for novel second-line therapies for NSCLC patients.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Lung cancer is a leading cause of cancer mortality worldwide.
- Immune checkpoint inhibitors (ICIs) combined with chemotherapy are first-line treatments for advanced non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGAs).
- Despite improved outcomes, primary or acquired resistance to these therapies is frequent, leading to disease progression and poor survival.
Purpose of the Study:
- To review current first- and second-line treatments for NSCLC without AGAs.
- To identify unmet needs in the second-line setting, including resistance mechanisms and limited treatment options.
- To discuss emerging therapies for patients progressing on first-line treatments.
Main Methods:
- Literature review of current treatments for NSCLC without AGAs.
- Analysis of unmet needs and resistance mechanisms.
- Overview of emerging therapeutic agents and their mechanisms of action.
Main Results:
- Current first-line treatments for NSCLC without AGAs include ICIs and platinum-based chemotherapy.
- Significant unmet needs exist in the second-line setting due to resistance and lack of effective options.
- Emerging therapies targeting various resistance mechanisms show promise for future treatment strategies.
Conclusions:
- Resistance to first-line therapy is a major challenge in advanced NSCLC without AGAs.
- Novel therapeutic agents are under investigation to overcome resistance and improve outcomes in the second-line setting and beyond.
- These emerging therapies have the potential to alter the standard of care for NSCLC patients who progress on initial treatment.
More Related Videos
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
09:38Establishing 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
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...