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Review
. 2023 Aug 30:10:1243531.
doi: 10.3389/fcvm.2023.1243531. eCollection 2023.

Revisiting treatment-related cardiotoxicity in patients with malignant lymphoma-a review and prospects for the future

Eva Rihackova  1 , Michal Rihacek  2   3   4 , Maria Vyskocilova  1 , Dalibor Valik  2   3   5 , Lubomir Elbl  1
Affiliations
Review

Revisiting treatment-related cardiotoxicity in patients with malignant lymphoma-a review and prospects for the future

Eva Rihackova et al. Front Cardiovasc Med. .

Abstract

Treatment of malignant lymphoma has for years been represented by many cardiotoxic agents especially anthracyclines, cyclophosphamide, and thoracic irradiation. Although they are in clinical practice for decades, the precise mechanism of cardiotoxicity and effective prevention is still part of the research. At this article we discuss most routinely used anti-cancer drugs in chemotherapeutic regiments for malignant lymphoma with the focus on novel insight on molecular mechanisms of cardiotoxicity. Understanding toxicity at molecular levels may unveil possible targets of cardioprotective supportive therapy or optimization of current therapeutic protocols. Additionally, we review novel specific targeted therapy and its challenges in cardio-oncology.

Keywords: cardiac adverse events; cardiotoxicity; chemotherapy; lymphoma; modern treatment; prevention.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of anthracycline-induced cardiotoxicity with highlighted possible therapeutic targets. Anthracycline cytotoxic effects in cell include DNA alterations [direct damage and processing alterations through inhibition of cardiac TOP2beta (14)], energy metabolism impairment, induction of apoptosis [via casp3, p53 and p38 pathway (25, 35, 39)], and decreased contractility [involvement of MURF1 pathway and myosin heavy chain degradation (56, 57)]. Cell parts illustrations were implemented from free Servier repository available at: https://smart.servier.com/.
Figure 2
Figure 2
Mechanism of CTX-induced cardiomyopathy and its possible pharmacoprevention. CTX cytotoxic properties are similar to those of anthracyclines to a certain degree as both drugs direct several similar cellular compartments including mitochondria (energy metabolism) (99) and myosin heavy chains (MURF1) (111). Moreover, CTX cardiac adverse events are mediated through signal impairment (METTL3 downregulation), vasospasm (inhibition of NOS), interstitial haemorrhage (induced through direct cell damage and formation of microthrombi), inflammation (upregulation of NF-kappa-B), oxidative stress and apoptosis (–105). Cell parts illustrations were implemented from free Servier repository available at: https://smart.servier.com/.
See this image and copyright information in PMC

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