Transformation to small cell lung cancer and activation of KRAS during long‑term erlotinib maintenance in a patient with non‑small cell lung cancer: A case report

  • Authors:
    • Yangchun Gu
    • Xiang Zhu
    • Baoshan Cao
    • Xue Wu
    • Xiaoling Tong
    • Yang W. Shao
    • Li Liang
  • View Affiliations

  • Published online on: March 28, 2019     https://doi.org/10.3892/ol.2019.10196
  • Pages: 5219-5223
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Abstract

Epidermal growth factor receptor (EGFR)‑positive non‑small cell lung cancer (non‑SCLC) benefits from first‑line treatment with first generation tyrosine kinase inhibitors (TKIs). However, drug resistance is inevitable through different mechanisms and is dominated by the acquisition of the T790M mutation within EGFR, which occurs in ~50% of cases. The present study reports the case of a patient originally diagnosed with stage IA lung adenocarcinoma, with a recurrent tumor lesion in each side of the lungs following the surgical removal of the primary tumor. Erlotinib treatment of the recurrent tumors eliminated the tumor on the right side of the lung and resulted in the histological transformation of the tumor on the left side to SCLC following 6 years of treatment. Genetic profiling of the SCLC lesions using targeted next‑generation sequencing identified different genetic alterations from the primary tumor, characterized by the newly acquired copy number loss of tumor protein p53 and transcriptional coreceptor 1, and the copy number gain of SRY‑box 2. Continuation of treatment with chemotherapy and erlotinib demonstrated moderate disease control for ~1 year prior to the outbreak of a new lung lesion. Liquid biopsy profiling of circulating tumor DNA revealed the acquisition of KRAS proto‑oncogene, GTPase (KRAS) p.G12C mutation, indicating the occurrence of another resistance mechanism to erlotinib. During erlotinib treatment, the lung adenocarcinoma progressed through two atypical mechanisms, notably from the transformation to SCLC and the acquisition of the KRAS mutation to surpass EGFR inhibition. However, the combinational and interchanging usage of chemotherapy and TKI resulted in persistent and effective disease control.
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June 2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Gu, Y., Zhu, X., Cao, B., Wu, X., Tong, X., Shao, Y.W., & Liang, L. (2019). Transformation to small cell lung cancer and activation of KRAS during long‑term erlotinib maintenance in a patient with non‑small cell lung cancer: A case report. Oncology Letters, 17, 5219-5223. https://doi.org/10.3892/ol.2019.10196
MLA
Gu, Y., Zhu, X., Cao, B., Wu, X., Tong, X., Shao, Y. W., Liang, L."Transformation to small cell lung cancer and activation of KRAS during long‑term erlotinib maintenance in a patient with non‑small cell lung cancer: A case report". Oncology Letters 17.6 (2019): 5219-5223.
Chicago
Gu, Y., Zhu, X., Cao, B., Wu, X., Tong, X., Shao, Y. W., Liang, L."Transformation to small cell lung cancer and activation of KRAS during long‑term erlotinib maintenance in a patient with non‑small cell lung cancer: A case report". Oncology Letters 17, no. 6 (2019): 5219-5223. https://doi.org/10.3892/ol.2019.10196