• 作者： Arpita Poddar, Farah Ahmady, Sushma R. Rao, Revati Sharma, George Kannourakis, Prashanth Prithviraj & Aparna Jayachandran
• 作者服務機構： 1.Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia 2.Federation University, Victoria, Australia 3.Fiona Elsey Cancer Research Institute, Victoria, Australia 4.RMIT University, Victoria, Australia
• 中文摘要：
• 英文摘要：
  Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.
• 中文關鍵字：
• 英文關鍵字： s Pregnancy associated plasma protein-A, Breast cancer, Triple negative breast cancer, Epithelialmesenchymal transition, Cancer therapy, Cancer biomarker, Immunotherapy