title: [Tumor resistance to HER2 inhibitors: the drug sedimentation concept].
abstract: Twenty years have passed between the discovery of oncogene HER2, the description of its implication in mammary carcinogenesis, and the development of specific targeted therapies. To date, trastuzumab and lapatinib are the two anti-HER2 targeted therapies commonly used, demonstrating therapeutic effects. Although their clinical efficacy seems to be exclusively related to the amplification of the HER2 gene or to the overexpression of the protein, these factors are not sufficient since tumors can develop resistance. Because of a better knowledge in those mechanisms of resistance, novel therapeutic agents could help to bypass them. How should these be used with respect to current anti-HER2 targeted therapies? Recent notions such as oncogene addiction, tumor cell dormancy and residual disease led us to propose a new entity that we named the "sedimentation strategy", in which distinct targeted approaches are summed during the treatment of metastatic breast cancer patients.
authors.affiliation: Centre René-Gauducheau, département d'oncologie médicale, boulevard Jacques-Monod, 44805 Saint-Herblain, Nantes Cedex, France. m-campone@nantes.fnclcc.fr
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Frenel
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Philippe
authors.initials: P
authors.lastname: Juin
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077341:Lapatinib; D058990:Molecular Targeted Therapy / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human