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Oncology Letters
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Print ISSN: 1792-1074 Online ISSN: 1792-1082
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October-2026 Volume 32 Issue 4

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International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Case Report Open Access

Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report

  • Authors:
    • Alizée Simon
    • Gautier Treffel
    • Guillaume Pax
    • Guillaume Gauchotte
    • Marie Husson
    • Idrissia Hanriot
    • Agnès Leroux
    • Jean-Louis Merlin
    • Alexandre Harlé
    • Pauline Gilson

  • View Affiliations / Copyright

    Affiliations: University of Lille, Inserm (French National Institute of Health and Medical Research), Lille Regional University Hospital Center, French National Centre for Scientific Research, Oscar Lambret Center, Joint Research Unit 9020‑CANTHER‑Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000 Lille, France, Department of Pulmonary Medicine, Nancy Regional University Hospital, 54511 Vandœuvre‑lès‑Nancy, France, Department of Biopathology, Lorraine Institute of Cancerology/Nancy Regional University Hospital, 54519 Vandœuvre‑lès‑Nancy, France
    Copyright: © Simon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 448
    |
    Published online on: August 5, 2026
       https://doi.org/10.3892/ol.2026.15803
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Abstract

ALK fusions occur in 3‑6% of lung cancers and confer sensitivity to ALK‑tyrosine kinase inhibitors. However, acquired resistance inevitably develops through multiple mechanisms, limiting the durability of the treatment response. The present report describes the case of a 36‑year‑old man with ALK‑rearranged lung adenocarcinoma treated with the second‑generation ALK‑tyrosine kinase inhibitor alectinib. At the time of disease progression, molecular analysis revealed the emergence of a KRAS mosaicism. The present report details the molecular evolution of the tumor, from the initial diagnosis to treatment failure. The current report illustrates a compelling mechanism of resistance to ALK inhibition driven by the synchronous emergence of multiple KRAS variants. While previous case reports have documented an isolated KRAS mutation as a potential resistance mechanism to ALK‑tyrosine kinase inhibitor therapy, to the best of our knowledge, this is the first report describing such extensive KRAS mosaicism upon failure of alectinib treatment. The present report highlights the importance of reevaluating the molecular profile of the cancer at the time of progression to accurately define the resistance pathway and develop rational therapeutic strategies capable of overcoming this resistance.

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Copy and paste a formatted citation
Spandidos Publications style
Simon A, Treffel G, Pax G, Gauchotte G, Husson M, Hanriot I, Leroux A, Merlin J, Harlé A, Gilson P, Gilson P, et al: Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report. Oncol Lett 32: 448, 2026.
APA
Simon, A., Treffel, G., Pax, G., Gauchotte, G., Husson, M., Hanriot, I. ... Gilson, P. (2026). Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report. Oncology Letters, 32, 448. https://doi.org/10.3892/ol.2026.15803
MLA
Simon, A., Treffel, G., Pax, G., Gauchotte, G., Husson, M., Hanriot, I., Leroux, A., Merlin, J., Harlé, A., Gilson, P."Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report". Oncology Letters 32.4 (2026): 448.
Chicago
Simon, A., Treffel, G., Pax, G., Gauchotte, G., Husson, M., Hanriot, I., Leroux, A., Merlin, J., Harlé, A., Gilson, P."Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report". Oncology Letters 32, no. 4 (2026): 448. https://doi.org/10.3892/ol.2026.15803
Copy and paste a formatted citation
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Spandidos Publications style
Simon A, Treffel G, Pax G, Gauchotte G, Husson M, Hanriot I, Leroux A, Merlin J, Harlé A, Gilson P, Gilson P, et al: Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report. Oncol Lett 32: 448, 2026.
APA
Simon, A., Treffel, G., Pax, G., Gauchotte, G., Husson, M., Hanriot, I. ... Gilson, P. (2026). Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report. Oncology Letters, 32, 448. https://doi.org/10.3892/ol.2026.15803
MLA
Simon, A., Treffel, G., Pax, G., Gauchotte, G., Husson, M., Hanriot, I., Leroux, A., Merlin, J., Harlé, A., Gilson, P."Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report". Oncology Letters 32.4 (2026): 448.
Chicago
Simon, A., Treffel, G., Pax, G., Gauchotte, G., Husson, M., Hanriot, I., Leroux, A., Merlin, J., Harlé, A., Gilson, P."Emergence of KRAS mosaicism with multiple variants during treatment with alectinib in ALK‑positive metastatic non‑small cell lung cancer: A case report". Oncology Letters 32, no. 4 (2026): 448. https://doi.org/10.3892/ol.2026.15803
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