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Ineffectiveness of Crizotinib in a Non-Small-Cell Lung Cancer with Novel ALK- LIMS1 Fusion: A Case Report
Junmei Shi1, Zhaohui Jia2, Zhiguo Zhou1
1Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
Abstract:
Anaplastic lymphoma kinase (ALK) rearrangements have been reported in 3-7% of non-small-cell lung cancers (NSCLC). ALK has been reported to be fused with a variety of genes in NSCLC. Significant clinical activity was achieved by ALK inhibitors in patients with NSCLC harbouring ALK translocations. We reported on a 48-year-old male Chinese patient with advanced lung adenocarcinoma harboring a novel ALK-LIMS1 who showed no response to crizotinib. The tissue was assayed by immunohistochemistry (IHC) for ALK and showed diffuse expression of ALK. Next-generation sequencing (NGS) was performed on the peripheral blood and tissue. The previous tumor tissue showed diffuse expression of ALK. Tissue and the later peripheral blood revealed a ALK- LIMS1 fusion. The patient failed to benefit from crizotinib (250 mg, twice a day), with a progression-free survival of two months. We identified a new ALK-LIMS1 fusion from an advanced lung adenocarcinoma which was primary resistant to crizotinib. Our case suggested that the coexistence of mutations and the non-dominant clone, as well as the rearrangement of ALK fusion, did not result in expressed ALK kinase domain that might lead to no response to ALK-TKIs.
Insights
A novel Anaplastic Lymphoma Kinase (ALK)-LIMS1 fusion in lung adenocarcinoma showed primary resistance to crizotinib. This suggests that certain ALK rearrangements may not lead to a responsive kinase domain for ALK-tyrosine kinase inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anaplastic Lymphoma Kinase (ALK) rearrangements occur in 3-7% of non-small-cell lung cancers (NSCLC).
- ALK inhibitors demonstrate significant clinical activity in NSCLC patients with ALK translocations.
- Various genes have been reported to fuse with ALK in NSCLC.
Observation:
- A 48-year-old Chinese male with advanced lung adenocarcinoma presented with a novel ALK-LIMS1 fusion.
- Immunohistochemistry (IHC) showed diffuse ALK expression in tumor tissue.
- Next-generation sequencing (NGS) confirmed the ALK-LIMS1 fusion in both tissue and peripheral blood.
Findings:
- The patient exhibited primary resistance to crizotinib, with a progression-free survival of two months.
- This case identified a new ALK-LIMS1 fusion in advanced lung adenocarcinoma.
- The ALK-LIMS1 fusion did not result in a responsive ALK kinase domain to crizotinib treatment.
Implications:
- The findings suggest that not all ALK rearrangements lead to sensitivity to ALK-tyrosine kinase inhibitors (TKIs).
- Coexisting mutations or non-dominant clones might influence treatment response.
- Further research is needed to understand the mechanisms of primary resistance to ALK-TKIs in NSCLC.
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