ArticleThe oncologist2026
Methylation-based liquid biopsy facilitates early detection of small cell transformation in ALK-rearranged non-small cell lung cancer.
Article in The oncologist, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a rare mechanism of resistance in anaplastic lymphoma kinase (ALK)-rearranged disease. Diagnosis is traditionally dependent on tissue biopsy, which may be limited by lesion accessibility and low disease burden. We report a case of ALK-rearranged lung adenocarcinoma that underwent small cell transformation, in which methylation-based circulating cell-free DNA (cfDNA) analysis detected a small cell lung cancer signature 5 months prior to tissue confirmation. Serial liquid biopsies demonstrated dynamic changes in tumor fraction and histologic composition that correlated with response to chemoradiation and continuation of ALK-directed therapy. This case highlights the potential utility of methylation-based liquid biopsy for early detection and longitudinal monitoring of histologic transformation in oncogene-driven NSCLC.
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