Abstract
BackgroundPatients 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.ResultsOur 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.MethodsWe 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.ConclusionAnalysis 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.
Highlights
Colorectal cancer (CRC) is the third most common cancer in the world
Analysis of plasma circulating tumor DNA (ctDNA) by digital polymerase chain reaction (PCR) could be useful for detecting HER2 amplification in patients with CRC who were resistant to anti-epidermal growth factor receptor (EGFR) antibody therapy
Plasma samples were obtained from 18 patients with histologically confirmed metastatic CRC who were being treated with cetuximab-based therapy
Summary
Colorectal cancer (CRC) is the third most common cancer in the world. Advances in systemic chemotherapies have led to significant improvements in survival for patients with metastatic CRC [1, 2]. Recent research efforts have focused on the development of agents targeting the epidermal growth factor receptor (EGFR), which is frequently overexpressed in colorectal cancer and contributes cancer cell proliferation, metastasis, and angiogenesis [3]. HER2 genomic amplification was shown to evolve in CRC tumors after acquisition of resistance to cetuximab, despite the absence of HER2 amplification prior to cetuximab therapy. This resistance could be overcome using HER2 inhibitors, such as trastuzumab and lapatinib. Patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS benefit from epidermal growth factor receptor (EGFR)-targeted therapy. 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
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