Abstract
Anaplastic lymphoma kinase (ALK) rearrangement occurs in 5% to 8% of patients with non-small cell lung cancer (NSCLC). More than 90 different ALK fusion partners have been discovered in NSCLC patients, and ALK tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib have achieved tumor responses in patients with advanced ALK-positive NSCLC. Here, we report the case of a patient with an advanced NSCLC carrying a novel serine/threonine kinase 3 (STK3)-ALK rearrangement, which was identified by targeted next-generation sequencing (NGS) and was confirmed by RNA sequencing. Anti-ALK immunohistochemistry (IHC) staining also revealed the high expression of ALK. The patient benefitted from alectinib treatment after experiencing crizotinib resistance and achieved an overall response to TKI of over 14 months. At the timepoint of submission of this manuscript, this patient is still receiving alectinib treatment with a good tolerance. This study provides meaningful insights into the potential treatment option for NSCLC patients with brain metastases harboring STK3-ALK fusions and highlights the advantages of NGS in rapidly identifying novel molecular targets.
Highlights
Anaplastic lymphoma kinase (ALK) rearrangement has been identified in up to 8% of non-small cell lung cancer (NSCLC) cases [1]
The serine/threonine kinase 3 (STK3)-ALK fusion was produced by a translocation event that fused the ALK kinase domain on chromosome 2, with the partial kinase domain of the STK3 gene on chromosome 8, linking intron 6 of STK3 to intron 20 of ALK (Figure 2C)
NSCLC patients who express a transforming fusion kinase can benefit from treatment with ALK-tyrosine kinase inhibitors (TKIs) [9]
Summary
Anaplastic lymphoma kinase (ALK) rearrangement has been identified in up to 8% of non-small cell lung cancer (NSCLC) cases [1]. As ALK-rearranged NSCLC patients respond to ALK tyrosine kinase inhibitors (TKIs), such as crizotinib, alectinib, and lorlatinib [3, 4], the identification of druggable ALK fusions is crucial for NSCLC treatment. Compared to traditional methods such as PCR and immunohistochemistry, next-generation sequencing (NGS) provides more comprehensive genomic information of cancers and increases the pace of identifying novel ALK fusions [2]. We report a patient with lung adenocarcinoma, harboring a novel serine/threonine kinase 3 (STK3)– ALK fusion, who was treated with crizotinib and alectinib and achieved an overall response of over 14 months. Case Report: STK3-ALK With Sensitivity to TKI in NSCLC associated with tumors and underscore the importance of genetic testing in revealing novel druggable genetic mutations. The PET-CT scan in April 2021 revealed decreased tumor lesions in her right lung and brain which indicated an SD (Figure 1A). The patient is currently receiving alectinib treatment with good tolerance
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