Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence

Pharmacol Ther. 2021 May;221:107751. doi: 10.1016/j.pharmthera.2020.107751. Epub 2020 Dec 1.

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.

Keywords: Senescence; cancer therapy; cardio-oncology; cardiotoxicity; cardiovascular diseases; doxorubicin; radiation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't