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BIOMARKER:

ALK V3a

i
Other names: NBLST3, CD246, Anaplastic Lymphoma Kinase, Anaplastic Lymphoma Kinase (Ki-1), CD246 Antigen, Mutant Anaplastic Lymphoma Kinase, ALK, ALK Receptor Tyrosine Kinase, Anaplastic Lymphoma Receptor Tyrosine Kinase, ALK Tyrosine Kinase Receptor
Entrez ID:
8ms
Real-World Outcome of Metastatic ALK-Positive Non-Small Cell Lung Cancer Treated with Tyrosine Kinase Inhibitors (IASLC-WCLC 2023)
In this retrospective study, we analyzed a real-life cohort of Swedish patients with advanced ALK-positive NSCLC treated at the Karolinska University Hospital in Stockholm to evaluate survival outcomes and resistance mechanisms of ALK TKIs. This retrospective study included 150 patients treated with at least one line of ALK TKI (crizotinib, ceritinib, alectinib, brigatinib or lorlatinib), from January 2009 to December 2021. Patients with advanced ALK-positive NSCLC have prolonged survival after the introduction of ALK TKIs with a median OS that exceeds 5 years when ALK TKIs are used in the first-line setting. Re-biopsies during treatment are needed to enhance our understanding of resistance mechanisms and the tumor dynamics that develop during ALK TKI therapy and to increase individualized management of this disease within precision medicine.
Real-world evidence • Clinical • Real-world • Metastases
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ALK (Anaplastic lymphoma kinase)
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ALK positive • ALK rearrangement • ALK fusion • ALK mutation • ALK V3a
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Oncomine™ Childhood Cancer Research Assay
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
1year
Clinicopathologic Features and Cytologic Correlation of ALK-rearranged Papillary Thyroid Carcinoma: A series of six cases (USCAP 2023)
In this case series, all six ALK -rearranged PTCs demonstrated a predominant follicular growth pattern and five of them were diagnosed as infiltrative follicular variant. The nuclear features were subtle and might be present in only focal areas, resulting in a significant rate of false negative diagnosis (33%, 2/6) in pre-operative FNA.
Clinical
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • STRN (Striatin)
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ALK positive • ALK rearrangement • ALK fusion • ALK V3a
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VENTANA ALK (D5F3) CDx Assay • Archer® FusionPlex® Lung Kit
over1year
Potential Therapeutic Strategy for EGFR-Mutant Lung Cancer With Concomitant EML4-ALK Rearrangement-Combination of EGFR Tyrosine Kinase Inhibitors and ALK Inhibitors. (PubMed, JTO Clin Res Rep)
PC-9_v3a-gef and PC-9_v3b-gef cells were resistant to gefitinib and ALK inhibitors alone, but ALK inhibitors enhanced gefitinib-induced cytotoxicity. Furthermore, combination treatment with osimertinib and ceritinib caused a decrease in liver tumor size of the patient with liver metastases. Our data suggest that combination treatment with EGFR and ALK inhibitors can be a therapeutic strategy for treating NSCLC with concomitant EGFR mutation and EML4-ALK rearrangement.
Journal
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EGFR (Epidermal growth factor receptor) • EML4 (EMAP Like 4)
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EGFR mutation • EGFR exon 19 deletion • EGFR expression • ALK rearrangement • ALK fusion • EML4-ALK variant 3 • EML4-ALK rearrangement • ALK V3a • ALK V3b • EML4-ALK variant 3a
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Tagrisso (osimertinib) • gefitinib • Zykadia (ceritinib)
2years
ALK fusion variant 3a/b, concomitant mutations, and high PD-L1 expression were associated with unfavorable clinical response to second-generation ALK TKIs in patients with advanced ALK-rearranged non-small cell lung cancer (GASTO 1061). (PubMed, Lung Cancer)
ALK fusion variant 3a/b, concomitant mutations, and high PD-L1 expression were associated with unfavorable clinical response to second-generation TKIs in ALK-rearranged NSCLC.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
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PD-L1 expression • PD-L1 overexpression • ALK positive • ALK rearrangement • ALK fusion • ALK mutation • ALK V3a
over2years
Deep RNA sequencing revealed fusion junctional heterogeneity may predict crizotinib treatment efficacy in ALK-rearranged non-small cell lung cancer. (PubMed, J Thorac Oncol)
Intratumoral EML4-ALK isoforms may predict the efficacy of targeted therapy in ALK-rearranged NSCLC. Temporal changes of intratumoral fusion isoforms may result from differential selection pressures that a drug might have on one isoform over another. Larger studies on fusion heterogeneity using RNA sequencing are warranted.
Clinical • Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK rearrangement • ALK fusion • ALK V3a • ALK V3b
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Xalkori (crizotinib)
over2years
Sensitivity of eight types of ALK fusion variant to alectinib in ALK-transformed cells. (PubMed, Anticancer Drugs)
There was no significant difference in the IC50 values between cells, with a <3.6-fold difference in responsiveness. In conclusion, these eight ALK variants had similar sensitivity to alectinib in vitro, indicating that it may not be possible to predict the response to alectinib just by determination of the ALK variant type in ALK fusion-positive NSCLCs.
Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • STRN (Striatin) • STAT3 (Signal Transducer And Activator Of Transcription 3) • KLC1 (Kinesin light chain 1)
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ALK positive • ALK fusion • ALK V3a
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Alecensa (alectinib)
almost3years
[VIRTUAL] Patient-derived lung cancer organoids for the selection of therapeutic options in an ALK-rearranged tumor. (ASCO 2021)
One patient was deemed as sensitive to carboplatin but tumor showed to be resistant...The patient started alectinib but showed progression after 12 months...Treatment was switched to brigatinib with no response...The In vitro results demonstrated no activity of lorlatinib but a strong response to crizotinib... We present clinical evidence that PDOs are an alternative tool in oncogenic addicted tumors helping to guide treatment decisions and increasing a more personalized sequential treatment approach.
Clinical • IO biomarker
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ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4)
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TP53 mutation • ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK C1156Y • ALK I1171T • ALK I1171 • ALK V3a • EML4-ALK C1156Y • EML4-ALK I1171T • EML4-ALK variant 3a
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Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)