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.
