HER2 as a novel therapeutic target for cervical cancer

// Doo-Yi Oh 1, 2, 3, * , Seokhwi Kim 1, * , Yoon-La Choi 1, 2, 3, * , Young Jae Cho 4, * , Ensel Oh 2, 3 , Jung-Joo Choi 4 , Kyungsoo Jung 3 , Ji-Young Song 2 , Suzie E. Ahn 2 , Byoung-Gie Kim 4 , Duk-Soo Bae 4 , Woong-Yang Park 3, 5 , Jeong-Won Lee 2, 3, 4, * , Sangyong Song 1, 2, * 1 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea 3 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea 4 Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Samsung Genome Institute, Samsung Medical Center, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Jeong-Won Lee, e-mail: garden.lee@samsung.com Sangyong Song, e-mail: yoda.song@samsung.com Keywords: HER2, cervical cancer, targeted therapy, patient-derived xenograft, trastuzumab Received: June 09, 2015 Accepted: September 11, 2015 Published: September 21, 2015 ABSTRACT Surgery and radiation are the current standard treatments for cervical cancer. However, there is no effective therapy for metastatic or recurrent cases, necessitating the identification of therapeutic targets. In order to create preclinical models for screening potential therapeutic targets, we established 14 patient-derived xenograft (PDX) models of cervical cancers using subrenal implantation methods. Serially passaged PDX tumors retained the histopathologic and genomic features of the original tumors. Among the 9 molecularly profiled cervical cancer patient samples, a HER2 -amplified tumor was detected by array comparative genomic hybridization and targeted next-generation sequencing. We confirmed HER2 overexpression in the tumor and serially passaged PDX. Co-administration of trastuzumab and lapatinib in the HER2-overexpressed PDX significantly inhibited tumor growth compared to the control. Thus, we established histopathologically and genomically homologous PDX models of cervical cancer using subrenal implantation. Furthermore, we propose HER2 inhibitor-based therapy for HER2 -amplified cervical cancer refractory to conventional therapy.