title: Cardio-oncology in targeting the HER receptor family: the puzzle of different cardiotoxicities of HER2 inhibitors.
abstract: The HER family of tyrosine kinase receptors includes several members that are clinically important targets in cancer therapies, in particular HER1 (the EGF receptor) and HER2, other members include HER3 and HER4. Trastuzumab, a humanized monoclonal antibody and lapatinib, a tyrosine kinase inhibitor, are drugs that target HER2, which is highly expressed in 20-30% of breast cancers. Trastuzumab is recommended as an adjuvant therapy for lymph node positive, HER2-positive breast cancers, or node-negative cancer with high-risk of recurrence, as well as in stage IV cancers. One serious side effect of trastuzumab is cardiomyocyte dysfunction, resulting in reduced heart contractile efficiency. The incidence of collateral effects on the heart with trastuzumab therapy increases in people with cardiovascular risk factors, heart disease and when combined with other chemotherapeutics. When cardiotoxicity was observed with trastuzumab, several studies have addressed potential cardiac damage of trastuzumab itself and lapatinib. The differences in cardiovascular effects of these two compounds are somewhat unexpected and suggest distinct mechanisms of action, which have clear implications in clinical application and prevention of cardiotoxicity in cardio-oncological approaches.
authors.affiliation: Oncology Research Division, Polo Scientifico e Tecnologico-IRCCS MultiMedica, Via Fantoli 16/15-20138, Milan, Italy. adriana.albini@multimedica.it
authors.forename: Adriana
authors.initials: A
authors.lastname: Albini
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cesana
authors.forename: Francesco
authors.initials: F
authors.lastname: Donatelli
authors.forename: Rosaria
authors.initials: R
authors.lastname: Cammarota
authors.forename: Eraldo O
authors.initials: EO
authors.lastname: Bucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Baravelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Anzà
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Noonan
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006321:Heart / Q000187:drug effects*; D006801:Humans; D000077341:Lapatinib; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000009:adverse effects / Q000494:pharmacology; D011929:Razoxane / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; D011929:Razoxane; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human