Reference Detail

Ref Type

PMID

(36506539)

Authors

Zhao J, Li X, Fan R, Qin Y, Wang Z, Wang B, Li S, Fan J, Wu X, Liu H, Guan Y, Liang Y, Zhang X, Guo Y

Title

Primary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C de novo mutation: A case report.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Frontiers in pharmacology	13		2022	1060460	Front Pharmacol

URL

Abstract Text

The effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with de novo ALK kinase domain mutations and ALK rearrangements who were not treated with ALK inhibitors have rarely been reported. Here, we report a case of primary drug resistance to first- and second-generation ALK inhibitors in a NSCLC patient with ALK-rearrangement. The next-generation sequencing test of the pathological biopsy showed that the de novo ALK kinase domain mutation F1174L-cis-S1189C may be the cause of primary drug resistance.

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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	S1189C	missense	unknown	ALK S1189C lies within the protein kinase domain of the Alk protein (UniProt.org). S1189C has been identified in the scientific literature (PMID: 36506539), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jan 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK ALK F1174L ALK S1189C	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK along with ALK F1174L in cis with ALK S1189C did not respond to second-line Zykadia (ceritinib) treatment (PMID: 36506539).	36506539
EML4 - ALK ALK F1174L ALK S1189C	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK along with ALK F1174L in cis with ALK S1189C did not respond to first-line Xalkori (crizotinib) treatment (PMID: 36506539).	36506539