Physiological, pharmacological and toxicological considerations of drug‐induced structural cardiac injury

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 tha...

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Bibliographic Details
Published in:British journal of pharmacology 2015-02, Vol.172 (4), p.957-974
Main Authors: 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, Park, B K
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - adverse effects
Cardiotoxicity - etiology
Cardiotoxicity - metabolism
Cardiotoxicity - pathology
Cardiotoxicity - physiopathology
Cardiotoxins - adverse effects
Cardiovascular Diseases - etiology
Cardiovascular Diseases - metabolism
Cardiovascular Diseases - pathology
Cardiovascular Diseases - physiopathology
Collaboration
Humans
Reviews
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Summary: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.
ISSN:0007-1188
1476-5381
DOI:10.1111/bph.12979