Abstract
Cancer treatment has been associated with accelerated aging that can lead to early-onset health complications typically experienced by older populations. In particular, cancer survivors have an increased risk of developing premature cardiovascular complications. In the last two decades, cellular senescence has been proposed as an important mechanism of premature cardiovascular diseases. Cancer treatments, specifically anthracyclines and radiation, have been shown to induce senescence in different types of cardiovascular cells. Additionally, clinical studies identified increased systemic markers of senescence in cancer survivors. Preclinical research has demonstrated the potential of several approaches to mitigate cancer therapy-induced senescence. However, strategies to prevent and/or treat therapy-induced cardiovascular senescence have not yet been translated to the clinic. In this review, we will discuss how therapy-induced senescence can contribute to cardiovascular complications. Thereafter, we will summarize the current in vitro, in vivo, and clinical evidence regarding cancer therapy-induced cardiovascular senescence. Then, we will discuss interventional strategies that have the potential to protect against therapy-induced cardiovascular senescence. To conclude, we will highlight challenges and future research directions to mitigate therapy-induced cardiovascular senescence in cancer survivors.
Original language | English (US) |
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Article number | 107751 |
Journal | Pharmacology and Therapeutics |
Volume | 221 |
DOIs | |
State | Published - May 2021 |
Bibliographical note
Funding Information:This research is supported by the National Heart, Lung, and Blood Institute, grant R01HL151740 (B.N.Z. and K.T.S.), the St. Baldrick's Foundation for Childhood Cancer (Award ID 638335, B.N.Z.); and the National Institutes of Health's National Center for Advancing Translational Sciences, grant UL1TR002494 (B.N.Z.). L.J.N. is supported by NIH: U01 ES-029603, R01 AG063543, U19 AG056278, R01 AG063543, and P01 AG062413.
Funding Information:
This research is supported by the National Heart, Lung, and Blood Institute , grant R01HL151740 (B.N.Z. and K.T.S.), the St. Baldrick’s Foundation for Childhood Cancer (Award ID 638335, B.N.Z.); and the National Institutes of Health’s National Center for Advancing Translational Sciences , grant UL1TR002494 (B.N.Z.). L.J.N. is supported by NIH : U01 ES-029603 , R01 AG063543 , U19 AG056278 , R01 AG063543 , and P01 AG062413 .
Publisher Copyright:
© 2020 Elsevier Inc.
Keywords
- Senescence
- cancer therapy
- cardio-oncology
- cardiotoxicity
- cardiovascular diseases
- doxorubicin
- radiation