CASE REPORT article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1613235
Case report: Metastatic Colorectal Cancer with ALK-CEP44 Fusion and Rapid Resistance Development Response to Alectinib in Metastatic Colorectal Cancer with multiple and functionally unclear ALK alterations -A Case Report
Provisionally accepted
- 1Spital Limmattal, Schlieren, Switzerland
- 2University Hospital Zürich, Zurich, Zürich, Switzerland
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Background: Colorectal cancer rarely harbors rearrangements in the ALK gene, and the therapeutic significance of non-canonical or functionally unclear ALK fusions remains poorly defined. We report a case of metastatic CRC with an ALK–CEP44 fusion not previously described in this tumor type, associated ALK overexpression, a notable clinical response to the ALK inhibitor alectinib, and rapid development of multiple ALK resistance mutations.Case Summary: A 60-year-old male patient was diagnosed with stage IIIA right-sided CRC. Six months after adjuvant chemotherapy, he developed liver metastases. Comprehensive molecular profiling revealed strong ALK expression, a novel ALK–CEP44 fusion predicted to lack a functional kinase domain, and additional ALK alterations. Palliative chemotherapy induced a temporary response. Upon progression, treatment with alectinib led to rapid clinical, radiological and biochemical improvement. However, disease progression recurred shortly thereafter, and next-generation sequencing revealed four resistance-associated ALK mutations. The patient ultimately died due to progressive liver failure.Conclusion: ALK-targeted therapy may provide benefit in selected CRC cases with atypical ALK alterations, even when the oncogenic role is uncertain. Comprehensive molecular profiling and timely therapeutic decisions are essential in managing such rare and complex cases.
Keywords: colorectal cancer, ALK gene mutation, targeted therapy, Drug Resistance, case report hat formatiert: Schriftart: (Standard) Cambria, 14 Pt., Fett, Kursiv
Received: 16 Apr 2025; Accepted: 29 May 2025.
Copyright: © 2025 Hofmann, Egger, Zoche, Wicki, Mehra and Potthast. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Silvan Hofmann, Spital Limmattal, Schlieren, Switzerland
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