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. 2022 Jun 23;5(3):762–793. doi: 10.20517/cdr.2022.18

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© The Author(s) 2022.

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Role of Family HER Pathway in osteosarcoma chemotherapy resistance. (A) Cisplatin resistance is associated with HER2 overexpression, PI3K/AKT activation and promotion p21 nuclear exclusion, favoring cell cycle arrest and proliferation. (B) Anti-EGFR therapy such as cetuximab and gefitinib sensitized osteosarcoma cells to DOX and MTX. (C) Afatinib a pan-HER Family inhibitor have an inhibition effect in osteosarcoma cell proliferation, migration an invasion. (D) Trastuzumab deruxtecan is an antibody-drug conjugated composed by anti-HER2 humanized monoclonal antibody and a topoisomerase I inhibitor as cytotoxic drug, that is now been tasted in clinical trials. AKT: Protein kinase B; DOX: doxorubicin; EGFR: epidermal growth factor receptor; ERK: extracellular signal-regulated kinase; HER: human epidermal growth factor; MTX: methotrexate; PI3K/AKT: phosphoinositide 3-kinase.