Multiple myeloma is a pathology of plasma cells, with one of the most common side effects of its treatment is
heart failure. In addition, cardiac
amyloidosis could cause
heart failure by itself. Even though mechanisms of cardiac
amyloidosis are known, and they involve lysosomal dysfunction,
reactive oxygen species (ROS) accumulation, and infiltrative effect by fibrils, there is no specific agent that could protect from these effects. While the molecular mechanism of
doxorubicin cardiotoxicity via
topoisomerase II β is established, the only FDA-approved agent for treatment is
dexrazoxane.
Liposomal doxorubicin can potentially improve response and decrease the development of
heart failure due to microscopic
liposomes that can accumulate and penetrate only
tumor vasculature. Supplements that enhance mitochondrial biogenesis are also shown to improve
doxorubicin-induced
cardiotoxicity. Other agents, such as
JR-311,
ICRF-193, and
ursolic acid, could potentially become new treatment options.
Proteasome inhibitors, novel agents, have significantly improved survival rates among
multiple myeloma patients. They act on a
proteasome system that is highly active in cardiomyocytes and activates various molecular cascades in malignant cells, as well as in the heart, through
nuclear factor kappa B (
NF-kB), endoplasmic reticulum (ER),
calcineurin-nuclear factor of activated T-cells (NFAT), and
adenosine monophosphate-activated
protein kinase (AMPKa)/autophagy pathways.
Metformin,
apremilast, and
rutin have shown positive results in animal studies and may become a promising
therapy as
cardioprotective agents. This article aims to highlight the main molecular mechanisms of
heart failure among patients with
multiple myeloma and potential treatment options to facilitate the development and research of new preventive strategies. Hence, this will have a positive impact on life expectancy in patients with
multiple myeloma.