Topics in Anti-Cancer Research

Topics in Anti-Cancer Research

Volume: 6

Indexed in: Chemical Abstracts, EBSCO, Ulrich's Periodicals Directory.

Topics in Anti-Cancer Research covers important advances on both experimental (preclinical) and clinical cancer research in drug development. The book series offers readers an insight into current ...
[view complete introduction]

US $
30

*(Excluding Mailing and Handling)



Effects of Inflammation, Mitochondria and Energy Metabolism in the Heart due to Cancer

Pp. 75-92 (18)

Thomas G. Ikonomidis, Timothy C. Tan and Patsie Polly

Abstract

Cancer cachexia is a paraneoplastic syndrome characterised by significant skeletal muscle wasting and cardiac atrophy. It occurs in 50% of patients with cancer and approximately 20% of cancer deaths are attributed to cachexia. Heart failure due to cancer cachexia is suggested to contribute to the high mortality rate and currently there is limited therapeutic intervention. The relationship between inflammation and energy metabolism as well as mitochondrial dysfunction in the heart in the context of cancer cachexia will be discussed. This chapter provides an understanding of potential, novel molecular mechanisms that could be of interest when considering therapeutic interventions for heart failure due to cancer cachexia. In summary, several interrelated molecular effects should be considered in cancer-induced cachexia in cardiomyocytes. TNF-α induced mitochondrial dysfunction may be important for the generation of ROS. IL-6 may induce an autophagic/mitophagic response as a result of downregulation of mitochondrial STAT3 due to mTOR suppression. An imbalance in mitochondrial dynamics may contribute to insulin-resistance and atrophy. Decreased expression of ANT1 may contribute to MPTP dysfunction and an altered energetic profile from adult to fetal metabolism. The effects of ANT1 expression in cardiac muscle during cancer cachexia is worth investigating in mouse models as discussed with reference to an ANT1 patent in this chapter. Furthermore, patents that are relevant for therapeutic strategies to ameliorate heart failure in cancer cachexia have also been discussed. Patents addressing interventions that could be applied to cancer cachexiainduced cardiac atrophy include: sodium selenite treatment, inhibitory agents of NADPH oxidase such as phycobilin, an AMPK inhibitor, modulation of mitochondrial biogenesis and modulation of mTOR. Understanding the underlying molecular mechanisms of mitochondrial dysfunction in cardiomyocytes during cancer cachexiainduced cardiac atrophy may reveal novel molecular targets for therapeutic intervention.

Keywords:

Cancer, cancer cachexia, cardiac atrophy, cardiomyocyte, energy metabolism, heart failure, inflammation, inflammatory cytokines, mitochondria, mitochondrial dynamics, mitochondrial dysfunction, mitophagy, muscle wasting.

Affiliation:

Mechanisms of Disease and Translational Research Group, Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney 2052, Australia.