title: Monitoring Trastuzumab Resistance and Cardiotoxicity: A Tale of Personalized Medicine.
abstract: While approval of trastuzumab, a recombinant monoclonal antibody directed against HER2, along with a diagnostic kit to detect breast cancers which are positive for HER2 overexpression, has advanced a new era of stratified and personalized medicine, it also created several challenges to our scientific and clinical practice. These problems include trastuzumab resistance and trastuzumab-induced cardiotoxicity. In this review, we will summarize data from the literature regarding mechanisms of trastuzumab resistance and trastuzumab-induced cardiotoxicity and present some promising model systems that may advance our understanding of these mechanisms. Our discussion will include development of circulating tumor cells and circulating tumor DNA for monitoring tumor burden, of patient-derived xenograft models for preclinical testing of novel therapies, and of novel therapeutic strategies for trastuzumab-resistance and possible integration of these strategies in the design of co-clinical studies for testing in relevant patient subpopulations.
authors.affiliation: Laboratory of Molecular Oncology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address: Milos.Dokmanovic@fda.hhs.gov.
authors.forename: Milos
authors.initials: M
authors.lastname: Dokmanovic
authors.affiliation: Laboratory of Molecular Oncology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address: Wen.Wu@fda.hhs.gov.
authors.forename: Wen Jin
authors.initials: WJ
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D066126:Cardiotoxicity / Q000150:complications / Q000209:etiology*; D004273:DNA, Neoplasm / Q000097:blood; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D057285:Precision Medicine; D000068878:Trastuzumab / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D000068878:Trastuzumab
keywords: Biomarkers; Breast cancer; Cardiotoxicity; HER2; HER2-positive breast cancer; Monoclonal antibody; Personalized medicine; Trastuzumab; Trastuzumab resistance; Trastuzumab-induced cardiotoxicity