Novel PLEC-EML4-ALK Double Fusion Underlying Crizotinib Resistance in a Metastatic Inflammatory Myofibroblastic Tumor: A Case Report
ALK fusions are frequent oncogenic drivers in inflammatory myofibroblastic tumors. Treatment with crizotinib is effective in fusion-positive patients; however, acquired resistance remains a challenge. Here, we present a case of EML4-ALK-positive metastatic inflammatory myofibroblastic tumor that ini...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
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| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364325000074 |
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| Summary: | ALK fusions are frequent oncogenic drivers in inflammatory myofibroblastic tumors. Treatment with crizotinib is effective in fusion-positive patients; however, acquired resistance remains a challenge. Here, we present a case of EML4-ALK-positive metastatic inflammatory myofibroblastic tumor that initially responded to crizotinib but developed resistance. The progressing lesion revealed the acquisition of a “double fusion” event in which EML4-ALK was additionally fused to PLEC to create a PLEC-EML4-ALK transcript. The double fusion was associated with an increase in ALK expression, mimicking the ALK fusion amplification that is a known mechanism of resistance to crizotinib in lung cancer. On transition to the more potent ALK inhibitor alectinib, the patient exhibited a dramatic response. Thus, the formation of a double fusion represents a novel and targetable mechanism of resistance to crizotinib. |
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| ISSN: | 2666-3643 |