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PMID (34376997)
Authors Yao B, Han X, Pang L, Xu C, Liu S, Cheng X, Chen J
Title Acquired ALK Resistance Mutations Identified from Liquid Biopsy in an ALK-Rearranged Squamous Cell Lung Cancer Patient Treated with Sequential ALK TKI Therapy: A Case Report.
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Abstract Text Anaplastic lymphoma kinase (ALK) rearrangement is extremely rare in lung squamous cell carcinoma (LSCC), and it remains controversial as to whether LSCC patients with ALK rearrangement can benefit from ALK tyrosine kinase inhibitors (TKIs). Here, we report an LSCC patient with ALK rearrangement who was treated with sequential ALK TKI therapies and experienced a clinical benefit of 35 months. Although the use of ALK TKIs showed clinical benefits, targeted next-generation sequencing (NGS) for dynamic monitoring of circulating tumor DNA (ctDNA) from patient plasma revealed the accumulation of ALK resistance mutations, which could provide valuable information in designing the treatment strategy. Our study highlights the importance of dynamic monitoring of ctDNA using NGS to discover tumor evolution to guide treatment decision-making and provides meaningful insights into the potential treatment options for ALK-positive LSCC patients.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK G1202R lung squamous cell carcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, third-line Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 7 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK and ALK G1202R (PMID: 34376997). 34376997
EML4 - ALK lung squamous cell carcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment with whole-brain radiotherapy resulted in a partial response with a progression-free survival of 17 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK (PMID: 34376997). 34376997
EML4 - ALK lung squamous cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response in the lung and partial response in the brain lesions in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, with a progression-free survival of 11 months (PMID: 34376997). 34376997
EML4 - ALK ALK G1202R lung squamous cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, who previously responded to Alunbrig (brigatinib) treatment (PMID: 34376997). 34376997