The same targeting antibody, but one carries a chemotherapy payload directly into the tumour cell. Enhertu is what happened when Herceptin was turned into an antibody-drug conjugate.
Herceptin is a HER2/neu receptor antagonist indicated in adults for: The treatment of HER2-overexpressing breast cancer. ( 1.1 , 1.2 ) The treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. ( 1.3 ) Select patients for therapy based on an FDA-authorized companion diagnostic for Herceptin ( 1 , 2.2 ). 1.1 Adjuvant Breast Cancer Herceptin is indicated in adults for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies (14.1) ] ) breast cancer as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel as part of a treatment regimen with docetaxel and carboplatin as a single agent following multi-modality anthracycline based therapy. Select patients for therapy based on an FDA-authorized companion diagnostic f…
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for: HER2-Positive Early Breast Cancer as neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP). ( 1.1 ) as adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment. ( 1.1 ) HER2-Positive Metastatic Breast Cancer in combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test. ( 1.2 ) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (…
12.1 Mechanism of Action The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Herceptin has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2. Herceptin is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro , Herceptin-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.
12.1 Mechanism of Action Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death.
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