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Updated: Sep 29, 2025

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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Multiple Genetic Alterations as Resistance Mechanism during Second-Line Lorlatinib for Advanced ALK-Rearranged Lung

Annamaria Catino1, Rosanna Lacalamita2, Simona De Summa2

  • 1Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy.

Diagnostics (Basel, Switzerland)
|March 25, 2022
PubMed

Insights

Newer ALK-TKI inhibitors are effective for advanced ALK-rearranged lung adenocarcinoma but resistance emerges. Reassessing tumor biomarkers during treatment is crucial for managing resistance to targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Second and third-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) demonstrate superior efficacy compared to crizotinib in advanced ALK-rearranged non-small cell lung cancer.
  • Despite advancements, acquired resistance to these newer ALK-TKIs, including lorlatinib, remains a significant clinical challenge, often involving complex resistance mechanisms.

Observation:

  • The case study focuses on a patient with advanced ALK-rearranged lung adenocarcinoma experiencing resistance to current ALK-TKI therapies.
  • Lorlatinib, a potent ALK-TKI, can be associated with diverse and intricate resistance pathways.

Findings:

  • Emergence of resistance mechanisms can compromise the sustained activity of even advanced-generation ALK-TKIs.
  • The study underscores the necessity of serial biomolecular profiling, utilizing both tissue and liquid biopsies, to understand evolving resistance patterns.

Implications:

  • Comprehensive assessment of resistance mechanisms is vital for optimizing treatment strategies in ALK-TKI-resistant lung cancer.
  • Identifying novel therapeutic targets or drug sequencing through detailed resistance profiling can improve patient outcomes and management.
Keywords:
ALK-rearranged lung cancercase reportlorlatinibresistance mechanisms

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