The role of senescence in cancer therapy-associated cardiovascular toxicity

Cardiovascular diseases (CVDs) and cancer are the two leading causes of global mortality. Cancer treatments, including radiotherapy and chemotherapy, can have severe cardiotoxic side effects, raising concerns for cancer patients and increasing the financial burden on healthcare systems. Recent studies have shown a link between cancer therapy-induced cardiotoxicity and cardiac senescence. Specifically, systemic cancer therapies are known to induce cardiac senescence, which may directly result in cardiac dysfunction or enhance the vulnerability of the heart to other stressors. Besides anthracyclines, newer, more targeted therapies such as tyrosine kinase inhibitors (TKIs) have also been shown to induce cardiac senescence. Cellular senescence is triggered by DNA damage, oncogene activation, reactive oxygen and nitrogen species, and other stressors, leading to the secretion of proinflammatory factors, increased oxidative stress, and disruption of normal cellular functions. Understanding the molecular mechanisms of cardiac senescence induced by cancer therapy is essential for attenuating or even preventing clinically overt cardiotoxicity using senotherapies such as senolytics and senomorphics. In this review, cancer therapies that are associated with CVDs are described with an emphasis on the potential role of cardiac senescence in the disease progression. In addition, the known mechanisms by which anthracyclines, particularly doxorubicin (DOX), radiotherapy, and TKIs lead to cardiac senescence are highlighted. Finally, recent and novel senotherapies for treating cellular senescence are discussed with a focus on targeting cardiac senescence following cancer treatment. The field remains in its early stages, with further research required to clarify how cancer treatments contribute to cardiotoxicity. At the same time, identifying senotherapies that can be safely combined with cancer drugs is essential for targeting cardiac senescence and protecting cardiac health in cancer patients.