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Characterizing Herbivore Resistance Mechanisms: Spittlebugs on Brachiaria spp. as an Example
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Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib

Niamh Coleman1, Andrew Wotherspoon2, Nadia Yousaf1

  • 1Lung Unit, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom.

Lung Cancer (Amsterdam, Netherlands)
|July 20, 2019
PubMed
Abstract

Insights

Small cell transformation is a resistance mechanism in ALK-positive lung cancer. Re-biopsy is recommended to identify neuroendocrine carcinoma transformation and guide treatment for ALK-rearranged NSCLC.

Area of Science:

  • Oncology
  • Translational Research
  • Genomics

Background:

  • Anaplastic Lymphoma Kinase (ALK)-rearranged Non-Small Cell Lung Cancer (NSCLC) often develops resistance to targeted therapies.
  • Small cell transformation is a known resistance mechanism in EGFR-mutant NSCLC but is less understood in ALK-rearranged NSCLC.

Observation:

  • A case of ALK-rearranged NSCLC is presented, where the patient progressed despite three lines of ALK-targeted therapies.
  • Acquired resistance to lorlatinib was observed, characterized by transformation to neuroendocrine carcinoma and acquisition of the ALK G1196A mutation.

Findings:

  • Neuroendocrine carcinoma transformation is a significant mechanism of acquired resistance to lorlatinib in ALK-rearranged NSCLC.
  • The study highlights a specific case demonstrating this transformation and a concurrent ALK mutation.

Implications:

  • Re-biopsy upon progression in ALK-positive NSCLC is crucial for accurate diagnosis and treatment selection, potentially offering more insights than liquid biopsies.
  • Understanding neuroendocrine transformation is vital for developing future therapeutic strategies against resistant ALK-rearranged NSCLC.
Keywords:
ALK positiveNSCLCNeuroendocrine transformationOncogene addictedSmall cell lung cancer

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