Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors

• Published in: Frontiers in cardiovascular medicine 2023-06, Vol.10, p.1186679
• Main Authors: Banerjee, Priyanka, Rosales, Julia Enterría, Chau, Khanh, Nguyen, Minh T H, Kotla, Sivareddy, Lin, Steven H, Deswal, Anita, Dantzer, Robert, Olmsted-Davis, Elizabeth A, Nguyen, Hung, Wang, Guangyu, Cooke, John P, Abe, Jun-Ichi, Le, Nhat-Tu
• Format: Article
• Language: English
• Subjects: atherosclerosis; Cardiovascular Medicine; disturbed flow; endoMT; senescence; sumoylation
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2023.1186679

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS phenotype hold promise as a therapeutic approach for managing atherosclerotic CVD in this population. This review aims to provide a mechanistic understanding of SAS induction in ECs and its contribution to atherosclerosis among cancer survivors. We delve into the mechanisms underlying EC senescence in response to disturbed flow and ionizing radiation, which play pivotal role in atherosclerosis and cancer. Key pathways, including p90RSK/TERF2IP, TGFβR1/SMAD, and BH4 signaling are explored as potential targets for cancer treatment. By comprehending the similarities and distinctions between different types of senescence and the associated pathways, we can pave the way for targeted interventions aim at enhancing the cardiovascular health of this vulnerable population. The insights gained from this review may facilitate the development of novel therapeutic strategies for managing atherosclerotic CVD in cancer survivors.