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An update on biomarkers for kinase inhibitor response in non-small-cell lung cancer
Bo Mi Ku1, Jong-Mu Sun2, Se-Hoon Lee2
1a Samsung Biomedical Research Institute, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
Introduction:
The discovery of activating genetic and their use as predictive biomarkers for targeted therapy, such as tyrosine kinase inhibitors (TKIs), has changed the treatment paradigm of non-small cell lung cancer (NSCLC). As a result, epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) TKIs have become the standard first-line treatment. Since then, other kinds of targetable oncogenic alterations have been identified in NSCLC. Several novel, molecularly-targeted TKIs have now achieved regulatory approval, while many others are currently in early- or late-phase clinical trial testing. These TKIs have significantly impacted and changed clinical outcomes for advanced NSCLC. Areas covered: In this review, the authors discuss recent evidence and progress in targeted therapies, especially small molecular tyrosine kinase inhibitors, matched with their biomarkers for the treatment of advanced NSCLC. Expert commentary: Although targeted therapies dramatically improve the outcome of patients with NSCLC harboring specific oncogenic alterations, molecular and clinical resistance almost invariably develops. New TKIs specifically active in molecular subgroups of NSCLC or the resistance setting have now been developed. The development of additional TKIs and rational combinations may further improve outcomes of NSCLC.
Insights
Targeted therapies, like tyrosine kinase inhibitors (TKIs), have transformed non-small cell lung cancer (NSCLC) treatment by targeting specific genetic alterations. Research continues to develop new TKIs and combinations to overcome resistance and improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Targeted therapies and biomarkers have revolutionized non-small cell lung cancer (NSCLC) treatment.
- Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are now standard first-line treatments for NSCLC.
- Numerous other targetable oncogenic alterations and novel TKIs are emerging for advanced NSCLC.
Purpose of the Study:
- To review recent advancements in targeted therapies, focusing on small molecular TKIs and their corresponding biomarkers for advanced NSCLC.
- To discuss the impact of these targeted therapies on clinical outcomes in advanced NSCLC.
- To highlight the development of new TKIs and combination strategies to address resistance.
Main Methods:
- Literature review of recent evidence and progress in targeted therapies for NSCLC.
- Analysis of molecularly-targeted TKIs and their predictive biomarkers.
- Discussion of clinical trial data for novel TKIs in NSCLC treatment.
Main Results:
- Targeted therapies, particularly TKIs, have significantly improved outcomes for advanced NSCLC patients with specific oncogenic alterations.
- Several novel TKIs have gained regulatory approval, with many more in clinical trials.
- Molecular and clinical resistance to targeted therapies is a common challenge in NSCLC treatment.
Conclusions:
- Targeted therapies have dramatically improved outcomes for NSCLC patients with specific genetic alterations.
- New TKIs are being developed for specific molecular subgroups and to overcome resistance.
- Further development of TKIs and rational combinations holds promise for improving NSCLC outcomes.
