Cardiovascular side effects of cancer therapies: A position statement from the Heart Failure Association of the European Society of Cardiology
Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.European Journal of Heart Failure (Impact Factor: 6.53). 01/2011; 13(1):1-10. DOI: 10.1093/eurjhf/hfq213
The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.
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- "Side effects are associated with the use of the conventional treatments in cancer due to low selectivity of the drugs on tumor cells, this results in reduction in quality of life in patients under treatment (Cella and Fallowfield, 2008; Mans et al., 2000; Eschenhagen et al., 2011). Modern medicine has advanced considerably, however , medicinal plants are still used in many parts of the world (Heinrich et al., 1998; Valerio and Gonzales, 2005; Choudhary et al., 2008; McClatchey et al., 2009). "
ABSTRACT: Two cucurbitacin-type triterpenes kinoin A (1) and kinoin B diglucoside (2) were isolated and character-ized by chromatographic and spectroscopic techniques from the root of Ibervillea sonorae. By MTT assaytheir antiproliferative activity was evaluated and only compound 1 was able to inhibit the growth ofHeLa, M12AK.C3F6, A549 and RAW 264.7 cancer cell lines with a IC50of 18.0, 31.4, 40.2, and 61.5 �M,respectively. L-929 cell line used as a control was more resistant to compound 1 at IC50values greaterthan 100 �M. Apoptosis induction was quantified for a double staining by Annexin V/propidium iodideusing flow cytometry, and it was observed that treatment of HeLa cells with compound 1 cause cell deathby apoptosis.
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- "LVEF: left ventricular ejection fraction. a Decrease in LVEF was defined as a decrease in the ejection fraction of 10 percentage points or more from baseline to an LVEF of less than 50 percent at any time   "
ABSTRACT: In recent years, a number of new molecules - commonly known as biological therapies - have been approved or are in late stages of regulatory evaluation for the treatment of advanced breast cancer. These innovative compounds have improved treatment efficacy and have probably contributed to the increase in survival length observed in some breast cancer subtypes. However, these agents are not deprived of toxicity, which can impair quality of life and may occasionally be life-threatening. In this article, we reviewed the most common toxicities associated with these drugs and provided a number of practical recommendations on their optimal clinical management.
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- "Given the limited regenerative capacity of the heart, cumulative toxicity may be explained by the progressive increase of cardiac cell loss. Cardiac cell stress (specifically oxidative stress induced by anthracyclines and many kinase inhibitors) activates apoptosis and necrosis via a mitochondrial pathway  . As mitochondria are a central component of intrinsic apoptotic and necrotic pathways, mitochondrial " effects " of anticancer drugs are to be an expected outcome of adverse interactions between the drug and cells  "
ABSTRACT: Anthracyclines remain the cornerstone of treatment in many malignancies but these agents have a cumulative dose relationship with cardiotoxicity. Development of cardiomyopathy and congestive heart failure induced by anthracyclines are typically dose-dependent, irreversible, and cumulative. Although past studies of cardiotoxicity have focused on anthracyclines, more recently interest has turned to anticancer drugs that target many proteins kinases, such as tyrosine kinases. An attractive model to explain the mechanism of this cardiotoxicity could be myocyte loss through cell death pathways. Inhibition of mitochondrial transition permeability is a valuable tool to prevent doxorubicin-induced cardiotoxicity. In response to anthracycline treatment, activation of several protein kinases, neuregulin/ErbB2 signaling, and transcriptional factors modify mitochondrial functions that determine cell death or survival through the modulation of mitochondrial membrane permeability. Cellular response to anthracyclines is also modulated by a myriad of transcriptional factors that influence cell fate. Several novel targeted chemotherapeutic agents have been associated with a small but worrying risk of left ventricular dysfunction. Agents such as trastuzumab and tyrosine kinase inhibitors can lead to cardiotoxicity that is fundamentally different from that caused by anthracyclines, whereas biological effects converge to the mitochondria as a critical target.
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