Cascade Downregulation of the HER Family by a Dual-Targeted Recombinant Protein-Drug Conjugate to Inhibit Tumor Growth and Metastasis

© 2022 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 34(2022), 23 vom: 20. Juni, Seite e2201558
1. Verfasser: Yuan, Yang (VerfasserIn)
Weitere Verfasser: Zhou, Sensen, Li, Cheng, Zhang, Xiaoke, Mao, Hui, Chen, Weizhi, Jiang, Xiqun
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article drug delivery epidermal growth factor receptor family epidermal growth factor receptor type 2 integrins recombinant proteins Antineoplastic Agents Integrins Recombinant Proteins Doxorubicin mehr... 80168379AG Receptor, ErbB-2 EC 2.7.10.1 Trastuzumab P188ANX8CK
Beschreibung
Zusammenfassung:© 2022 Wiley-VCH GmbH.
Human epidermal growth factor receptor type 2 (HER2)-targeted therapy can significantly improve the outcome of patients with HER2 positive cancer. However, relapse after this treatment remains a great challenge in the clinic due to tumor resistance, in which the HER network induces constitutive signal transduction. In addition, integrin receptors in the tumor extracellular matrix can mitigate the therapeutic effect of inhibitors to the growth factors receptors and tyrosine kinases. Here, the development of a recombinant protein (RP-HI) and its drug conjugates (RPDC-HI) to target both HER2 and integrin is reported. When simultaneously blocking HER2 and integrin by RP-HI, functions of the HER family and their interactions with the integrin are disrupted by downregulated expressions of HER family members, leading to inhibition of several downstream signal pathways. In combination with targeted delivery of the anticancer agent, doxorubicin (DOX), RPDC-HI significantly improves the tumor inhibition efficacy to 97.5% in treating HER2-positive breast cancer, comparing to 34.3% for free DOX. RPDC-HI shows even better antitumor efficiency than a monoclonal antibody, trastuzumab, when treating larger tumors. The developed dual-targeted RPDC platform offers a new and promising strategy for treating HER2-positive patients with synergistic therapeutic effects against tumor resistance to the conventional HER2-targeted treatment
Beschreibung:Date Completed 10.06.2022
Date Revised 10.06.2022
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202201558