HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer

Naoki Takegawa, Kimio Yonesaka, Kazuko Sakai, Hiroto Ueda, Satomi Watanabe, Yoshikane Nonagase, Tatsuya Okuno, Masayuki Takeda, Osamu Maenishi, Junji Tsurutani, Taroh Satoh, Isamu Okamoto, Kazuto Nishio, Takao Tamura, Kazuhiko Nakagawa

    Research output: Contribution to journalArticlepeer-review

    55 Citations (Scopus)

    Abstract

    Background: Patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS benefit from epidermal growth factor receptor (EGFR)-targeted therapy. However, patients who are treated with anti-EGFR antibodies will eventually develop the resistance to those agents. HER2 amplification is one of the mechanisms conferring resistance to anti-EGFR antibody therapy and could therefore be a potential therapeutic target. The aim of this study was to detect HER2 amplification in circulating tumor DNA (ctDNA) from patients with CRC and acquired resistance to anti-EGFR antibody therapy Results: Our data showed that 22% (4/18) of patients in the cohort exhibited HER2 amplification. One of these patients was found to be positive for HER2 amplification in matched tumor specimens collected after cetuximab therapy, at which point the patient had acquired cetuximab resistance, despite being negative for HER2 amplification prior to therapy. Methods: We analyzed plasma ctDNA using digital polymerase chain reaction (PCR) from 18 patients with CRC, who had been treated with anti-EGFR antibody-based therapy (cetuximab) and subsequently acquired resistant cetuximab. HER2 gene copy number was analyzed using fluorescence in situ hybridization in tumor samples before and after acquisition of resistance to cetuximab-based therapy. Conclusion: Analysis of plasma ctDNA by digital PCR could be useful for detecting HER2 amplification in patients with CRC who were resistant to anti-EGFR antibody therapy.

    Original languageEnglish
    Pages (from-to)3453-3460
    Number of pages8
    JournalOncotarget
    Volume7
    Issue number3
    DOIs
    Publication statusPublished - 2016

    All Science Journal Classification (ASJC) codes

    • Oncology

    Fingerprint

    Dive into the research topics of 'HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer'. Together they form a unique fingerprint.

    Cite this