2. Academic Validation
  3. A Novel c-MET-Targeting Antibody-Drug Conjugate for Pancreatic Cancer

A Novel c-MET-Targeting Antibody-Drug Conjugate for Pancreatic Cancer

  • Front Oncol. 2021 Mar 17:11:634881. doi: 10.3389/fonc.2021.634881.
Yangbing Jin 1 2,  Zehui Zhang 1 2,  Siyi Zou 1 2,  Fanlu Li 1 2,  Hao Chen 1 2,  Chenghong Peng 1 2,  Xiaxing Deng 1 2,  Chenlei Wen 1 2,  Baiyong Shen 1 2,  Qian Zhan 1 2
Affiliations

Affiliations

  • 1 Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
PMID: 33816276 DOI: 10.3389/fonc.2021.634881
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated death in the United States and has a 5-year survival rate of <4%. Although much effort has been invested in the research and development of pancreatic Cancer drugs over the past 30 years, due to the lack of effective targetable carcinogenic drivers, no new targeted therapies that can improve patient prognosis have been approved for clinical use. SHR-A1403 is a new c-mesenchymal-epithelial transition factor (c-MET) antibody-drug conjugate that can be used for the targeted treatment of PDAC with high c-MET expression. This study reports for the first time the application prospects of SHR-A1403 in preclinical models of PDAC. SHR-A1403 significantly inhibited the proliferation, migration, and invasion of pancreatic Cancer cells and induced cell cycle arrest and Apoptosis. These changes were caused by inhibition of intracellular Cholesterol biosynthesis by SHR-A1403. Therefore, targeting c-MET through SHR-A1403 showed strong preclinical anti-tumour efficacy in pancreatic Cancer. Our work suggests the potential application of c-MET-targeted antibody-drug conjugate treatment for PDAC in clinical practise.

Keywords

SHR-A1403; anti-tumour; c-Met antibody-drug conjugate; cholesterol metabolism; pancreatic ductal adenocarcinoma.

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