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Interactive Case Discussions: Serial NGS in ALK+ Lung Adenocarcinoma Navigating Resistance Through Longitudinal Molecular Profiling
Prof. Darren Lim presents a longitudinal ALK-positive lung cancer case demonstrating how serial tissue and plasma NGS can identify evolving resistance mechanisms, optimize sequential targeted therapy, and extend clinical benefit over multiple lines of treatment.
In this interactive case discussion, Prof. Darren Lim follows the molecular journey of a patient with metastatic ALK-positive lung adenocarcinoma treated over more than eight years. The case illustrates how serial genomic profiling guided multiple treatment decisions by identifying evolving resistance mutations throughout successive lines of ALK tyrosine kinase inhibitor (TKI) therapy.
The presentation demonstrates the complementary roles of tissue and plasma NGS. While tissue biopsy confirmed dominant resistance mutations, plasma-based liquid biopsy revealed a broader landscape of co-existing resistance mechanisms, better reflecting tumor heterogeneity and informing rational treatment sequencing. The case also highlights how persistent resistance clones can explain treatment failure following TKI rechallenge and underscores the importance of genomic reassessment at every disease progression.
Looking ahead, Prof. Lim discusses how emerging resistance patterns are shaping future therapeutic strategies, including fourth-generation ALK inhibitors and biomarker-driven clinical trials. The session reinforces serial molecular profiling as an essential component of personalized treatment planning for patients with ALK-positive NSCLC.
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