title: Physiological, pharmacological and toxicological considerations of drug-induced structural cardiac injury.
abstract: The incidence of drug-induced structural cardiotoxicity, which may lead to heart failure, has been recognized in association with the use of anthracycline anti-cancer drugs for many years, but has also been shown to occur following treatment with the new generation of targeted anti-cancer agents that inhibit one or more receptor or non-receptor tyrosine kinases, serine/threonine kinases as well as several classes of non-oncology agents. A workshop organized by the Medical Research Council Centre for Drug Safety Science (University of Liverpool) on 5 September 2013 and attended by industry, academia and regulatory representatives, was designed to gain a better understanding of the gaps in the field of structural cardiotoxicity that can be addressed through collaborative efforts. Specific recommendations from the workshop for future collaborative activities included: greater efforts to identify predictive (i) preclinical; and (ii) clinical biomarkers of early cardiovascular injury; (iii) improved understanding of comparative physiology/pathophysiology and the clinical predictivity of current preclinical in vivo models; (iv) the identification and use of a set of cardiotoxic reference compounds for comparative profiling in improved animal and human cellular models; (v) more sharing of data (through publication/consortia arrangements) on target-related toxicities; (vi) strategies to develop cardio-protective agents; and (vii) closer interactions between preclinical scientists and clinicians to help ensure best translational efforts.
authors.affiliation: MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cross
authors.forename: B R
authors.initials: BR
authors.lastname: Berridge
authors.forename: P J M
authors.initials: PJ
authors.lastname: Clements
authors.forename: L
authors.initials: L
authors.lastname: Cove-Smith
authors.forename: T L
authors.initials: TL
authors.lastname: Force
authors.forename: P
authors.initials: P
authors.lastname: Hoffmann
authors.forename: M
authors.initials: M
authors.lastname: Holbrook
authors.forename: A R
authors.initials: AR
authors.lastname: Lyon
authors.forename: H R
authors.initials: HR
authors.lastname: Mellor
authors.forename: A A
authors.initials: AA
authors.lastname: Norris
authors.forename: M
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: J D
authors.initials: JD
authors.lastname: Tugwood
authors.forename: J E
authors.initials: JE
authors.lastname: Sidaway
authors.forename: B K
authors.initials: BK
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D066126:Cardiotoxicity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D054715:Cardiotoxins / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D054715:Cardiotoxins