2. Academic Validation
  3. The anti-ErbB2 antibody H2-18 and the pan-PI3K inhibitor GDC-0941 effectively inhibit trastuzumab-resistant ErbB2-overexpressing breast cancer

The anti-ErbB2 antibody H2-18 and the pan-PI3K inhibitor GDC-0941 effectively inhibit trastuzumab-resistant ErbB2-overexpressing breast cancer

  • Oncotarget. 2017 May 16;8(32):52877-52888. doi: 10.18632/oncotarget.17907.
Lingfei Wang # 1 2,  Xiaojie Yu # 2,  Chao Wang # 2,  Shujun Pan # 3,  Beibei Liang 1,  Yajun Zhang 2,  Xiaodan Chong 2,  Yanchun Meng 4,  Jian Dong 5,  Yirong Zhao 2,  Yang Yang 2,  Huajing Wang 2,  Jie Gao 6,  Huafeng Wei 1 2,  Jian Zhao 1 2,  Hao Wang 2,  Chaohua Hu 7,  Wenze Xiao 8,  Bohua Li 1 2
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
  • 2 International Joint Cancer Institute, Second Military Medical University, Shanghai 200433, China.
  • 3 Hangzhou Sanatorium of People's Liberation Army, Hangzhou 310007, China.
  • 4 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai 200032, China.
  • 5 Department of Vascular Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
  • 6 Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai 200433, China.
  • 7 Department of General Surgery, Xiaogan Central Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 432000, China.
  • 8 Department of Rheumatology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.
  • # Contributed equally.
PMID: 28881779 DOI: 10.18632/oncotarget.17907
Abstract

Trastuzumab, an anti-ErbB2 humanized antibody, brings benefit to patients with ErbB2-amplified metastatic breast cancers. However, the resistance to trastuzumab is common. Our previously reported H2-18, an anti-ErbB2 antibody, potently induced programmed cell death in trastuzumab-resistant breast Cancer cells. Here, we aim to investigate the antitumor efficacy of H2-18 in combination with the pan-PI3K inhibitor GDC-0941 in trastuzumab-resistant breast Cancer cell lines. The results showed that H2-18 and GDC-0941 synergistically inhibited the in vitro proliferation of BT-474, SKBR-3, HCC-1954 and HCC-1419 breast Cancer cells. H2-18 plus GDC-0941 showed significantly enhanced programmed cell death-inducing activity compared with each drug used alone. The combination of H2-18 and GDC-0941 did not increase the effect of single agent on ROS production, cell cycle and ErbB2 signaling. Importantly, the in vivo antitumor efficacy of H2-18 plus GDC-0941 was superior to that of single agent. Thus, the enhanced in vivo antitumor efficacy of H2-18 plus GDC-0941 may mainly be attributable to its increased programmed cell death-inducing activity. Collectively, H2-18 plus GDC-0941 could effectively inhibit tumor growth, suggesting the potential to be translated into clinic as an efficient strategy for ErbB2-overexpressing breast cancers.

Keywords

GDC-0941; anti-ErbB2 antibody; breast cancer; programmed cell death; trastuzumab resistance.

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