Reference Detail

Ref Type

Journal Article

PMID

(39267820)

Authors

Cheng X, Liu J, Hu Q, Gao Y, Zhou L

Title

A novel secondary ALK gene mutation which resistant to second-generation TKIs: a case report and literature review.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Frontiers in oncology	14		2024	1430350	Front Oncol

URL

Abstract Text

Adenocarcinoma with positive echinoderm microtubule-associated protein-like 4 gene and anaplastic lymphoma kinase (EML4-ALK) gene fusion accounts for 3-7% of lung cancer cases and can be targeted with ALK tyrosine kinase inhibitors (TKIs). Second-generation TKIs are the standard of care for targeted populations, especially those with central nervous system (CNS) metastasis. However, most patients eventually experience disease progression because of drug resistance caused by multiple mechanisms, predominantly secondary mutations.We present a female advanced non-small cell lung cancer (NSCLC) case with positive EML4-ALK gene fusion, in which disease progression occurred in only 3 months after first-line treatment with alectinib. Two secondary mutations were detected by next-generation sequencing; one was V1180L located in exon 23, and the other was E803Q located in exon 14, which was a novel mutation that had never been reported. Ensartinib and ceritinib were administered as second-line and third-line treatments. However, the response to these TKIs was poor, and her overall survival was only 7 months.The secondary mutation E803Q located in exon 14 seems resistant to most second-generation ALK-TKIs. If there is an opportunity, the efficacy of the third-generation ALK-TKI loratinib should be tested.

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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
ALK	E803Q	missense	unknown	ALK E803Q lies within the extracellular domain of the Alk protein (UniProt.org). E803Q has been identified in the scientific literature (PMID: 39267820), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK ALK E803Q ALK V1180L	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK E803Q and V1180L were identified in post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20), who previously achieved a partial response on Alecensa (alectinib) treatment (PMID: 39267820).	39267820