Related Experiment Video
Updated: Jun 28, 2025
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Navigating resistance to ALK inhibitors in the lorlatinib era: a comprehensive perspective on NSCLC
Maria Gemelli1, Adriana Albini2, Gianpiero Catalano3
1Medical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milan, Italy.
Introduction:
The emergence of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC) has revolutionized targeted therapy. This dynamic landscape, featuring novel ALK inhibitors and combination therapies, necessitates a profound understanding of resistance mechanisms for effective treatment strategies. Recognizing two primary categories - on-target and off-target resistance - underscores the need for comprehensive assessment.
Areas Covered:
This review delves into the intricacies of resistance to ALK inhibitors, exploring complexities in identification and management. Molecular testing, pivotal for early detection and accurate diagnosis, forms the foundation for patient stratification and resistance management. The literature search methodology involved comprehensive exploration of Pubmed and Embase. The multifaceted perspective encompasses new therapeutic horizons, ongoing clinical trials, and their clinical implications post the recent approval of lorlatinib.
Expert Opinion:
Our expert opinion encapsulates the critical importance of understanding resistance mechanisms in the context of ALK inhibitors for shaping successful treatment approaches. With a focus on molecular testing and comprehensive assessment, this review contributes valuable insights to the evolving landscape of NSCLC therapy.
Insights
Understanding resistance to anaplastic lymphoma kinase (ALK) inhibitors is crucial for treating non-small cell lung cancer (NSCLC). This review details resistance mechanisms, molecular testing, and new therapies for improved patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Anaplastic lymphoma kinase (ALK) rearrangements are key drivers in non-small cell lung cancer (NSCLC).
- Targeted therapies with ALK inhibitors have transformed NSCLC treatment.
- Emergence of resistance mechanisms necessitates continuous research and updated strategies.
Purpose of the Study:
- To review resistance mechanisms to ALK inhibitors in NSCLC.
- To explore identification and management strategies for ALK inhibitor resistance.
- To discuss the role of molecular testing and novel therapeutic approaches.
Main Methods:
- Comprehensive literature search of Pubmed and Embase databases.
- Analysis of resistance mechanisms, including on-target and off-target resistance.
- Review of current and emerging ALK inhibitors and combination therapies.
Main Results:
- Resistance to ALK inhibitors is complex, involving on-target and off-target mechanisms.
- Molecular testing is essential for diagnosing resistance and guiding treatment selection.
- Novel therapeutic strategies and ongoing clinical trials offer new hope for patients.
Conclusions:
- Understanding ALK inhibitor resistance is critical for optimizing NSCLC treatment.
- Molecular profiling and comprehensive assessment are key to managing resistance.
- The field is rapidly evolving with new agents and therapeutic combinations.
More Related Videos
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
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...