1. Physiological, pharmacological and toxicological considerations of drug-induced structural cardiac injury.
- Author
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Cross, M J, Berridge, B R, Clements, P J M, Cove ‐ Smith, L, Force, T L, Hoffmann, P, Holbrook, M, Lyon, A R, Mellor, H R, Norris, A A, Pirmohamed, M, Tugwood, J D, Sidaway, J E, and Park, B K
- Subjects
PHARMACOLOGY ,CARDIOTOXICITY ,DRUG side effects ,HEART injuries ,HEART failure treatment ,ANTHRACYCLINES ,ANTINEOPLASTIC agents ,THERAPEUTICS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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