210
Views
1
CrossRef citations to date
0
Altmetric
Review

Anthracycline chemotherapy, Vascular Dysfunction and Cognitive Impairment: Burgeoning Topics and Future Directions

& ORCID Icon
Pages 547-566 | Received 09 Sep 2022, Accepted 17 Oct 2022, Published online: 10 Nov 2022

References

  • Benjamin EJ , ViraniSS, CallawayCWet al. Heart Disease and Stroke Statistics-2018 update: a report from the American Heart Association. Circulation, 137(12), e67–e492 (2018).
  • Paterson DI , WiebeN, CheungWYet al. Incident cardiovascular disease among adults with cancer: a population-based cohort study. JACC CardioOncol., 4(1), 85–94 (2022).
  • Aboumsallem JP , MoslehiJ, de BoerRA. Reverse cardio-oncology: cancer development in patients with cardiovascular disease. J. Am. Heart Assoc., 9(2), e013754 (2020).
  • Valero-Elizondo J , ChouairiF, KheraRet al. Atherosclerotic cardiovascular disease, cancer, and financial toxicity among adults in the United States. JACC CardioOncol., 3(2), 236–246 (2021).
  • Roth GA , MensahGA, JohnsonCOet al. Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J. Am. Coll. Cardiol., 76(25), 2982–3021 (2020).
  • Cardiovascular diseases. World Health Organization (2021). https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1
  • Guzik A , BushnellC. Stroke epidemiology and risk factor management. Continuum (Minneap Minn), 23(1, Cerebrovascular Disease), 15–39 (2017).
  • Groenewegen A , RuttenFH, MosterdA, HoesAW. Epidemiology of heart failure. Eur. J. Heart Fail., 22(8), 1342–1356 (2020).
  • Ovbiagele B , Nguyen-HuynhMN. Stroke epidemiology: advancing our understanding of disease mechanism and therapy. Neurotherapeutics, 8(3), 319–329 (2011).
  • Roy PS , SaikiaBJ. Cancer and cure: a critical analysis. Indian J. Cancer, 53(3), 441–442 (2016).
  • What is Cancer? In: National Cancer Institute.National Institutes of Health (2021). https://www.cancer.gov/about-cancer/understanding/what-is-cancer#:~:text=Cancer%20is%20a%20disease%20in,up%20of%20trillions%20of%20cells
  • Golemis EA , ScheetP, BeckTNet al. Molecular mechanisms of the preventable causes of cancer in the United States. Genes Dev., 32(13-14), 868–902 (2018).
  • Lewandowska AM , RudzkiM, RudzkiS, LewandowskiT, LaskowskaB. Environmental risk factors for cancer - review paper. Ann. Agric. Environ. Med., 26(1), 1–7 (2019).
  • Seals DR , JusticeJN, LaRoccaTJ. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J. Physiol., 594(8), 2001–2024 (2016).
  • Heart Disease Facts . Centers for Disease Control and Prevention (2022). https://www.cdc.gov/heartdisease/facts.htm
  • Health Topics - Heart disease and heart attack. In: Office of the Associate Director for Policy and Strategy.Center for Disease Control and Prevention (2022). https://www.cdc.gov/policy/polaris/healthtopics/heartdisease/index.html
  • Santucci C , CarioliG, BertuccioPet al. Progress in cancer mortality, incidence, and survival: a global overview. Eur. J. Cancer Prev., 29(5), 367–381 (2020).
  • Cancer Data and Statistics. In: Cancer.Centers for Disease Control and Prevention (2022). https://www.cdc.gov/cancer/dcpc/data/index.htm
  • Halpern MT , YabroffKR. Prevalence of outpatient cancer treatment in the United States: estimates from the Medical Panel Expenditures Survey (MEPS). Cancer Invest., 26(6), 647–651 (2008).
  • Ewald JA , DesotelleJA, WildingG, JarrardDF. Therapy-induced senescence in cancer. J. Natl Cancer Inst., 102(20), 1536–1546 (2010).
  • Schmitt CA , WangB, DemariaM. Senescence and cancer - role and therapeutic opportunities. Nat. Rev. Clin. Oncol., 19(10), 619–636 (2022).
  • Meredith AM , DassCR. Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism. J. Pharm. Pharmacol., 68(6), 729–741 (2016).
  • Zamel ON , InocianEP, AlshehryAS, TumalaRB, PatalagsaJG, AlsalehKA. Quality of life among breast and colon cancer patients before and after first-cycle chemotherapy. J. Holist. Nurs., 39(2), 116–125 (2021).
  • Jacobs JM , ReamME, PensakNet al. Patient Experiences With Oral Chemotherapy: Adherence, Symptoms, and Quality of Life. J. Natl Compr. Canc. Netw., 17(3), 221–228 (2019).
  • Institute NC . Cancer Statistics.National Institutes of Health (2020). https://www.cancer.gov/about-cancer/understanding/statistics
  • Minotti G , MennaP, SalvatorelliE, CairoG, GianniL. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev., 56(2), 185–229 (2004).
  • Kaklamani VG , GradisharWJ. Epirubicin versus doxorubicin: which is the anthracycline of choice for the treatment of breast cancer?Clin. Breast Cancer, 4(Suppl. 1), S26–S33 (2003).
  • Fujita N , FujitaK, KimSJet al. Response-guided omission of anthracycline in patients with HER2-positive early breast cancer treated with neoadjuvant taxane and trastuzumab: 5-year follow-up of prognostic study using propensity score matching. Oncology, 100(5), 257–266 (2022).
  • Gewirtz DA . A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol., 57(7), 727–741 (1999).
  • Meinardi MT , GietemaJA, van VeldhuisenDJ, vander Graaf WT, de VriesEG, SleijferDT. Long-term chemotherapy-related cardiovascular morbidity. Cancer Treat. Rev., 26(6), 429–447 (2000).
  • Khanna A , PequenoP, GuptaSet al. Increased risk of all cardiovascular disease subtypes among childhood cancer survivors: population-based matched cohort study. Circulation, 140(12), 1041–1043 (2019).
  • Ganz PA , GoodwinPJ. Breast cancer survivorship: where are we today?Adv. Exp. Med. Biol., 862, 1–8 (2015).
  • Chatterjee K , ZhangJ, HonboN, KarlinerJS. Doxorubicin cardiomyopathy. Cardiology, 115(2), 155–162 (2010).
  • Bhagat A , KleinermanES. Anthracycline-induced cardiotoxicity: causes, mechanisms, and prevention. Adv. Exp. Med. Biol., 1257, 181–192 (2020).
  • Vuong JT , Stein-MerlobAF, ChengRK, YangEH. Novel therapeutics for anthracycline induced cardiotoxicity. Front. Cardiovasc. Med., 9, 863314 (2022).
  • Luu AZ , ChowdhuryB, Al-OmranM, TeohH, HessDA, VermaS. Role of endothelium in doxorubicin-induced cardiomyopathy. JACC Basic Transl. Sci., 3(6), 861–870 (2018).
  • Lakatta EG , LevyD. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation, 107(1), 139–146 (2003).
  • Parr SK , LiangJ, SchadlerKL, GilchristSC, SteeleCC, AdeCJ. Anticancer therapy-related increases in arterial stiffness: a systematic review and meta-analysis. J. Am. Heart Assoc., 9(14), e015598 (2020).
  • Budinskaya K , PuchnerováV, SvačinováJet al. Non-invasive assessment of vascular system function and damage induced by anthracycline treatment in the pediatric cancer survivors. Physiol. Res., 66(Suppl. 4), S553–S560 (2017).
  • Terwoord JD , BeyerAM, GuttermanDD. Endothelial dysfunction as a complication of anti-cancer therapy. Pharmacol. Ther., 237, 108116 (2022).
  • Adji A , O’RourkeMF, NamasivayamM. Arterial stiffness its assessment, prognostic value, and implications for treatment. Am. J. Hypertens., 24(1), 5–17 (2011).
  • Mitchell GF , HwangSJ, VasanRSet al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation, 121(4), 505–511 (2010).
  • Cahill PA , RedmondEM. Vascular endothelium - Gatekeeper of vessel health. Atherosclerosis, 248, 97–109 (2016).
  • Celermajer DS , SorensenKE, BullC, RobinsonJ, DeanfieldJE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J. Am. Coll. Cardiol., 24(6), 1468–1474 (1994).
  • Cosentino F , RubattuS, SavoiaC, VenturelliV, PagannonneE, VolpeM. Endothelial dysfunction and stroke. J. Cardiovasc. Pharmacol., 38(Suppl. 2), S75–S78 (2001).
  • Seals DR , JablonskiKL, DonatoAJ. Aging and vascular endothelial function in humans. Clin. Sci. (Lond)., 120(9), 357–375 (2011).
  • Clayton ZS , BruntVE, HuttonDAet al. Doxorubicin-induced oxidative stress and endothelial dysfunction in conduit arteries is prevented by mitochondrial-specific antioxidant treatment. JACC CardioOncol., 2(3), 475–488 (2020).
  • Gioscia-Ryan RA , ClaytonZS, ZiglerMCet al. Lifelong voluntary aerobic exercise prevents age- and Western diet- induced vascular dysfunction, mitochondrial oxidative stress and inflammation in mice. J. Physiol., 599(3), 911–925 (2021).
  • Rossman MJ , Gioscia-RyanRA, Santos-ParkerJRet al. Inorganic nitrite supplementation improves endothelial function with aging: translational evidence for suppression of mitochondria-derived oxidative stress. Hypertension, 77(4), 1212–1222 (2021).
  • Brunt VE , Gioscia-RyanRA, CassoAGet al. Trimethylamine-N-oxide promotes age-related vascular oxidative stress and endothelial dysfunction in mice and healthy humans. Hypertension, 76(1), 101–112 (2020).
  • Green D . Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function. J. Appl. Physiol. (1985), 99(3), 1233–1234 (2005).
  • Tabas I , García-CardeñaG, OwensGK. Recent insights into the cellular biology of atherosclerosis. J. Cell Biol., 209(1), 13–22 (2015).
  • Chirinos JA , SegersP, HughesT, TownsendR. Large-artery stiffness in health and disease: JACC state-of-the-art review. J. Am. Coll. Cardiol., 74(9), 1237–1263 (2019).
  • Waldstein SR , RiceSC, ThayerJF, NajjarSS, ScuteriA, ZondermanAB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore longitudinal study of aging. Hypertension, 51(1), 99–104 (2008).
  • Pase MP , BeiserA, HimaliJJet al. Aortic stiffness and the risk of incident mild cognitive impairment and dementia. Stroke, 47(9), 2256–2261 (2016).
  • Wang MC , TsaiWC, ChenJY, HuangJJ. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am. J. Kidney Dis., 45(3), 494–501 (2005).
  • Butlin M , TanI, SpronckB, AvolioAP. Measuring arterial stiffness in animal experimental studies. Arterioscler. Thromb. Vasc. Biol., 40(5), 1068–1077 (2020).
  • Tanaka H , DinennoFA, MonahanKD, ClevengerCM, DeSouzaCA, SealsDR. Aging, habitual exercise, and dynamic arterial compliance. Circulation, 102(11), 1270–1275 (2000).
  • Dengel DR , NessKK, GlasserSP, WilliamsonEB, BakerKS, GurneyJG. Endothelial function in young adult survivors of childhood acute lymphoblastic leukemia. J. Pediatr. Hematol. Oncol., 30(1), 20–25 (2008).
  • Jang WJ , ChoiDY, JeonIS. Vascular endothelial dysfunction after anthracyclines treatment in children with acute lymphoblastic leukemia. Korean J. Pediatr., 56(3), 130–134 (2013).
  • Lee K , KangI, MackWJet al. Effects of high-intensity interval training on vascular endothelial function and vascular wall thickness in breast cancer patients receiving anthracycline-based chemotherapy: a randomized pilot study. Breast Cancer Res. Treat., 177(2), 477–485 (2019).
  • Steeghs N , RabelinkTJ, op’tRoodt Jet al. Reversibility of capillary density after discontinuation of bevacizumab treatment. Ann. Oncol., 21(5), 1100–1105 (2010).
  • Chow AY , ChinC, DahlG, RosenthalDN. Anthracyclines cause endothelial injury in pediatric cancer patients: a pilot study. J. Clin. Oncol., 24(6), 925–928 (2006).
  • Jenei Z , BárdiE, MagyarMT, HorváthA, ParaghG, KissC. Anthracycline causes impaired vascular endothelial function and aortic stiffness in long term survivors of childhood cancer. Pathol. Oncol. Res., 19(3), 375–383 (2013).
  • Jones LW , HaykowskyM, PeddleCJet al. Cardiovascular risk profile of patients with HER2/neu-positive breast cancer treated with anthracycline-taxane-containing adjuvant chemotherapy and/or trastuzumab. Cancer Epidemiol. Biomarkers Prev., 16(5), 1026–1031 (2007).
  • Chaosuwannakit N , D’AgostinoR, HamiltonCAet al. Aortic stiffness increases upon receipt of anthracycline chemotherapy. J. Clin. Oncol., 28(1), 166–172 (2010).
  • Rimessi A , PreviatiM, NigroF, WieckowskiMR, PintonP. Mitochondrial reactive oxygen species and inflammation: molecular mechanisms, diseases and promising therapies. Int. J. Biochem. Cell Biol., 81(Pt B), 281–293 (2016).
  • Wallace KB , SardãoVA, OliveiraPJ. Mitochondrial determinants of doxorubicin-induced cardiomyopathy. Circ. Res., 126(7), 926–941 (2020).
  • Rossman MJ , Santos-ParkerJR, StewardCACet al. Chronic supplementation with a mitochondrial antioxidant (MitoQ) improves vascular function in healthy older adults. Hypertension, 71(6), 1056–1063 (2018).
  • Bikomeye JC , TerwoordJM, SantosJH, BeyerAM. Emerging mitochondrial signaling mechanisms in cardio-oncology: beyond oxidative stress. Am. J. Physiol. Heart Circ. Physiol., 323(4), H702–H720 (2022).
  • McCarthy CG , WenceslauCF, GoulopoulouSet al. Circulating mitochondrial DNA and Toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats. Cardiovasc. Res., 107(1), 119–130 (2015).
  • Clayton ZS , BruntVE, HuttonDAet al. Tumor necrosis factor alpha-mediated inflammation and remodeling of the extracellular matrix underlies aortic stiffening induced by the common chemotherapeutic agent doxorubicin. Hypertension, 77(5), 1581–1590 (2021).
  • Moreau KL , DeaneKD, MeditzAL, KohrtWM. Tumor necrosis factor-α inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. Atherosclerosis, 230(2), 390–396 (2013).
  • Galarraga B , KhanF, KumarP, PullarT, BelchJJ. Etanercept improves inflammation-associated arterial stiffness in rheumatoid arthritis. Rheumatology (Oxford), 48(11), 1418–1423 (2009).
  • Clayton ZS , HuttonDA, MahoneySA, SealsDR. Anthracycline chemotherapy-mediated vascular dysfunction as a model of accelerated vascular aging. Aging Cancer, 2(1-2), 45–69 (2021).
  • Russo M , BonoE, GhigoA. The interplay between autophagy and senescence in anthracycline cardiotoxicity. Curr. Heart Fail. Rep., 18(4), 180–190 (2021).
  • LaRocca TJ , HensonGD, ThorburnA, SindlerAL, PierceGL, SealsDR. Translational evidence that impaired autophagy contributes to arterial ageing. J. Physiol., 590(14), 3305–3316 (2012).
  • Prasanna PG , CitrinDE, HildesheimJet al. Therapy-induced senescence: opportunities to improve anticancer therapy. J. Natl Cancer Inst., 113(10), 1285–1298 (2021).
  • Demaria M , O’LearyMN, ChangJet al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov., 7(2), 165–176 (2017).
  • Freund A , OrjaloAV, DesprezPY, CampisiJ. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med., 16(5), 238–246 (2010).
  • Blaser H , DostertC, MakTW, BrennerD. TNF and ROS crosstalk in inflammation. Trends Cell Biol., 26(4), 249–261 (2016).
  • Demaria M , OhtaniN, YoussefSAet al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell., 31(6), 722–733 (2014).
  • Hutton D , BruntV, MahoneySet al. Cellular senescence mediates doxorubicin-induced arterial dysfunction via activation of mitochondrial oxidative stress and the mammalian target of rapamycin. FASEB J., 35(S1), (2021).
  • Mahoney S , HuttonD, RossmanMet al. Late-life treatment with the senolytic ABT-263 reverses aortic stiffening and improves endothelial function with aging. FASEB J., 35(S1), (2021).
  • Mahoney S , VenkatasubramanianR, RossmanMet al. Fisetin supplementation improves age-related vascular endothelial function by suppressing cellular senescence and mitochondrial oxidative stress. FASEB J., 36(S1), (2022).
  • Mounier NM , Abdel-MagedAE, WahdanSA, GadAM, AzabSS. Chemotherapy-induced cognitive impairment (CICI): an overview of etiology and pathogenesis. Life Sci., 258, 118071 (2020).
  • Aretouli E , BrandtJ. Everyday functioning in mild cognitive impairment and its relationship with executive cognition. Int. J. Geriatr. Psychiatry, 25(3), 224–233 (2010).
  • Rajan KB , WeuveJ, BarnesLL, McAninchEA, WilsonRS, EvansDA. Population estimate of people with clinical Alzheimer’s disease and mild cognitive impairment in the United States (2020–2060). Alzheimers Dement., 17(12), 1966–1975 (2021).
  • Sanford AM . Mild cognitive impairment. Clin. Geriatr. Med., 33(3), 325–337 (2017).
  • Jongsiriyanyong S , LimpawattanaP. Mild cognitive impairment in clinical practice: a review article. Am. J. Alzheimers Dis. Other Demen., 33(8), 500–507 (2018).
  • Ton TGN , DeLeireT, MaySGet al. The financial burden and health care utilization patterns associated with amnestic mild cognitive impairment. Alzheimers Dement., 13(3), 217–224 (2017).
  • Cascella M , DiNapoli R, CarboneD, CuomoGF, BimonteS, MuzioMR. Chemotherapy-related cognitive impairment: mechanisms, clinical features and research perspectives. Recenti. Prog. Med., 109(11), 523–530 (2018).
  • Graff-Radford J . Vascular cognitive impairment. Continuum (Minneap Minn)., 25(1), 147–164 (2019).
  • Iadecola C , DueringM, HachinskiVet al. Vascular cognitive impairment and dementia: JACC scientific expert panel. J. Am. Coll. Cardiol., 73(25), 3326–3344 (2019).
  • Csipo T , LipeczA, FulopGAet al. Age-related decline in peripheral vascular health predicts cognitive impairment. Geroscience, 41(2), 125–136 (2019).
  • Watson NL , Sutton-TyrrellK, RosanoCet al. Arterial stiffness and cognitive decline in well-functioning older adults. J. Gerontol. A Biol. Sci. Med. Sci., 66(12), 1336–1342 (2011).
  • Gorelick PB , CountsSE, NyenhuisD. Vascular cognitive impairment and dementia. Biochim. Biophys. Acta, 1862(5), 860–868 (2016).
  • Osterlundh G , BjureJ, LanneringB, KjellmerI, UvebrantP, MárkyI. Regional cerebral blood flow and neuron-specific enolase in cerebrospinal fluid in children with acute lymphoblastic leukemia during induction treatment. J. Pediatr. Hematol. Oncol., 21(5), 378–383 (1999).
  • Bailey TG , KleinT, MenesesALet al. Cerebrovascular function and its association with systemic artery function and stiffness in older adults with and without mild cognitive impairment. Eur. J. Appl. Physiol., 122(8), 1843–1856 (2022).
  • White Z , ParrS, TurpinV-R, HammondS, AdeC. Abstract 14119: aortic stiffness is associated with cognitive decline and cardiovascular disease manifestation in cancer survivors. Circulation, 144(A14119), (2021).
  • Hullinger R , PuglielliL. Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease. Behav. Brain Res., 322(Pt B), 191–205 (2017).
  • Young ML , FranklinJL. The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice. Mol. Cell. Neurosci., 101, 103409 (2019).
  • Cavalier AN , ClaytonZS, HuttonDAet al. Accelerated aging of the brain transcriptome by the common chemotherapeutic doxorubicin. Exp. Gerontol., 152, 111451 (2021).
  • Hirai K , AlievG, NunomuraAet al. Mitochondrial abnormalities in Alzheimer’s disease. J. Neurosci., 21(9), 3017–3023 (2001).
  • Hajjar I , HayekSS, GoldsteinFC, MartinG, JonesDP, QuyyumiA. Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study. J. Neuroinflamm., 15(1), 17 (2018).
  • Mecocci P , PolidoriMC. Antioxidant clinical trials in mild cognitive impairment and Alzheimer’s disease. Biochim. Biophys. Acta, 1822(5), 631–638 (2012).
  • Wichmann MA , CruickshanksKJ, CarlssonCMet al. Long-term systemic inflammation and cognitive impairment in a population-based cohort. J. Am. Geriatr. Soc., 62(9), 1683–1691 (2014).
  • Vivek S , NelsonHH, PrizmentAE, FaulJ, CrimminsEM, ThyagarajanB. Cross sectional association between cytomegalovirus seropositivity, inflammation and cognitive impairment in elderly cancer survivors. Cancer Cause Control, 33(1), 81–90 (2022).
  • Calsolaro V , EdisonP. Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement., 12(6), 719–732 (2016).
  • Ogrodnik M , EvansSA, FielderEet al. Whole-body senescent cell clearance alleviates age-related brain inflammation and cognitive impairment in mice. Aging Cell, 20(2), e13296 (2021).
  • Yabluchanskiy A , TarantiniS, BalasubramanianPet al. Pharmacological or genetic depletion of senescent astrocytes prevents whole brain irradiation-induced impairment of neurovascular coupling responses protecting cognitive function in mice. Geroscience, 42(2), 409–428 (2020).
  • Bussian TJ , AzizA, MeyerCF, SwensonBL, van DeursenJM, BakerDJ. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature, 562(7728), 578–582 (2018).
  • Poole DC , BehnkeBJ, MuschTI. The role of vascular function on exercise capacity in health and disease. J. Physiol., 599(3), 889–910 (2021).
  • Giza DE , IliescuG, HassanS, MarmagkiolisK, IliescuC. Cancer as a risk factor for cardiovascular disease. Curr. Oncol. Rep., 19(6), 39 (2017).
  • Darby SC , McGaleP, TaylorCW, PetoR. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol., 6(8), 557–565 (2005).
  • Ponnusamy L , MahalingaiahPKS, SinghKP. Treatment schedule and estrogen receptor-status influence acquisition of doxorubicin resistance in breast cancer cells. Eur. J. Pharm. Sci., 104, 424–433 (2017).
  • Pritchard JE , DillonPM, ConawayMR, SilvaCM, ParsonsSJ. A mechanistic study of the effect of doxorubicin/adriamycin on the estrogen response in a breast cancer model. Oncology, 83(6), 305–320 (2012).
  • Kohli S , GriggsJJ, RoscoeJAet al. Self-reported cognitive impairment in patients with cancer. J. Oncol. Pract., 3(2), 54–59 (2007).
  • Philpot RM , FickenM, WeckerL. Doxorubicin and cyclophosphamide lead to long-lasting impairment of spatial memory in female, but not male mice. Behav. Brain Res., 307, 165–175 (2016).
  • Stachenfeld NS , MazureCM. Precision medicine requires understanding how both sex and gender influence health. Cell, 185(10), 1619–1622 (2022).
  • Santos JD , Oliveira-NetoJT, BarrosPRet al. Th17 cell-linked mechanisms mediate vascular dysfunction induced by testosterone in a mouse model of gender-affirming hormone therapy. Am. J. Physiol. Heart Circ. Physiol., 323(2), H322–H335 (2022).
  • Yuan C , ParekhH, AllegraC, GeorgeTJ, StarrJS. 5-FU induced cardiotoxicity: case series and review of the literature. Cardiooncology, 5, 13 (2019).
  • Bansal N , AdamsMJ, GanatraSet al. Strategies to prevent anthracycline-induced cardiotoxicity in cancer survivors. Cardiooncology, 5, 18 (2019).
  • Zheng H , DimayugaC, HudaihedA, KatzSD. Effect of dexrazoxane on homocysteine-induced endothelial dysfunction in normal subjects. Arterioscler. Thromb. Vasc. Biol., 22(7), E15–18 (2002).
  • DeVan AE , EskurzaI, PierceGLet al. Regular aerobic exercise protects against impaired fasting plasma glucose-associated vascular endothelial dysfunction with aging. Clin. Sci. (Lond)., 124(5), 325–331 (2013).
  • Durrant JR , SealsDR, ConnellMLet al. Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. J. Physiol., 587(Pt 13), 3271–3285 (2009).
  • Gioscia-Ryan RA , BattsonML, CuevasLM, ZiglerMC, SindlerAL, SealsDR. Voluntary aerobic exercise increases arterial resilience and mitochondrial health with aging in mice. Aging (Albany NY), 8(11), 2897–2914 (2016).
  • Lesniewski LA , DurrantJR, ConnellMLet al. Aerobic exercise reverses arterial inflammation with aging in mice. Am. J. Physiol. Heart Circ. Physiol., 301(3), H1025–1032 (2011).
  • Lesniewski LA , ZiglerML, DurrantJRet al. Aging compounds western diet-associated large artery endothelial dysfunction in mice: prevention by voluntary aerobic exercise. Exp. Gerontol., 48(11), 1218–1225 (2013).
  • Seals DR , EdwardF. Adolph Distinguished Lecture: the remarkable anti-aging effects of aerobic exercise on systemic arteries. J. Appl. Physiol. (1985), 117(5), 425–439 (2014).
  • Guadagni V , DrogosLL, TyndallAVet al. Aerobic exercise improves cognition and cerebrovascular regulation in older adults. Neurology, 94(21), e2245–e2257 (2020).
  • Nuzum H , StickelA, CoronaM, ZellerM, MelroseRJ, WilkinsSS. Potential benefits of physical activity in MCI and dementia. Behav. Neurol., 2020, 7807856 (2020).
  • Musanti R , ChaoYY, CollinsK. Fitness and quality of life outcomes of cancer survivor participants in a community exercise program. J. Adv. Pract. Oncol., 10(1), 24–37 (2019).
  • Beaudry RI , LiangY, BoytonSTet al. Meta-analysis of exercise training on vascular endothelial function in cancer survivors. Integr. Cancer Ther., 17(2), 192–199 (2018).
  • Mandolesi L , PolverinoA, MontuoriSet al. Effects of physical exercise on cognitive functioning and wellbeing: biological and psychological benefits. Front. Psychol., 9, 509 (2018).
  • Campbell KL , KamJWY, Neil-SztramkoSEet al. Effect of aerobic exercise on cancer-associated cognitive impairment: a proof-of-concept RCT. Psychooncology, 27(1), 53–60 (2018).
  • Winocur G , WojtowiczJM, HuangJ, TannockIF. Physical exercise prevents suppression of hippocampal neurogenesis and reduces cognitive impairment in chemotherapy-treated rats. Psychopharmacology (Berl)., 231(11), 2311–2320 (2014).
  • Montaño-Rojas LS , Romero-PérezEM, Medina-PérezC, Reguera-GarcíaMM, de PazJA. Resistance training in breast cancer survivors: a systematic review of exercise programs. Int. J. Environ. Res. Public Health, 17(18), (2020).
  • Lee K , TripathyD, Demark-WahnefriedWet al. Effect of aerobic and resistance exercise intervention on cardiovascular disease risk in women with early-stage breast cancer: a randomized clinical trial. JAMA Oncol., 5(5), 710–714 (2019).
  • Ng AH , Ngo-HuangA, VidalMet al. Exercise barriers and adherence to recommendations in patients with cancer. JCO Oncol. Pract., 17(7), e972–e981 (2021).
  • Schmitz KH , CourneyaKS, MatthewsCet al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med. Sci. Sports Exerc., 42(7), 1409–1426 (2010).
  • Thong MSY , van NoordenCJF, SteindorfK, ArndtV. Cancer-related fatigue: causes and current treatment options. Curr. Treat. Options Oncol., 21(2), 17 (2020).
  • Stutts WC . Physical activity determinants in adults. Perceived benefits, barriers, and self efficacy. AAOHN J., 50(11), 499–507 (2002).
  • El Ansari W , LovellG. Barriers to exercise in younger and older non-exercising adult women: a cross sectional study in London, United Kingdom. Int. J. Environ. Res. Public Health, 6(4), 1443–1455 (2009).
  • Craighead DH , HeinbockelTC, FreebergKAet al. Time-efficient inspiratory muscle strength training lowers blood pressure and improves endothelial function, no bioavailability, and oxidative stress in midlife/older adults with above-normal blood pressure. J Am Heart Assoc., 10(13), e020980 (2021).
  • Freeberg K , HeinbockelT, RossmanMet al. High-resistance inspiratory muscle strength training improves cerebrovascular function in midlife/older adults. FASEB J., 35(S1), (2021).
  • Brunt VE , HowardMJ, FranciscoMA, ElyBR, MinsonCT. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. J. Physiol., 594(18), 5329–5342 (2016).
  • Brunt V , RosenbergH, BazzoniAet al. Passive heat therapy lowers systolic blood pressure and improves vascular endothelial function in healthy older adults. FASEB J., 33(S1), 829.822–829.822 (2019).
  • Von Schulze AT , DengF, MorrisJK, GeigerPC. Heat therapy: possible benefits for cognitive function and the aging brain. J. Appl. Physiol. (1985), 129(6), 1468–1476 (2020).
  • Haendeler J , HoffmannJ, DiehlJFet al. Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells. Circ. Res., 94(6), 768–775 (2004).
  • Matsushita H , ChangE, GlassfordAJ, CookeJP, ChiuCP, TsaoPS. eNOS activity is reduced in senescent human endothelial cells: preservation by hTERT immortalization. Circ. Res., 89(9), 793–798 (2001).
  • Sato I , MoritaI, KajiK, IkedaM, NagaoM, MurotaS. Reduction of nitric oxide producing activity associated with in vitro aging in cultured human umbilical vein endothelial cell. Biochem. Biophys. Res. Commun., 195(2), 1070–1076 (1993).
  • Xin MG , ZhangJ, BlockER, PatelJM. Senescence-enhanced oxidative stress is associated with deficiency of mitochondrial cytochrome c oxidase in vascular endothelial cells. Mech. Ageing Dev., 124(8-9), 911–919 (2003).
  • Yoon HJ , ChoSW, AhnBW, YangSY. Alterations in the activity and expression of endothelial NO synthase in aged human endothelial cells. Mech. Ageing Dev., 131(2), 119–123 (2010).
  • Yousefzadeh MJ , ZhuY, McGowanSJet al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18–28 (2018).
  • Verdoorn BP , EvansTK, HansonGJet al. Fisetin for COVID-19 in skilled nursing facilities: senolytic trials in the COVID era. J. Am. Geriatr. Soc., 69(11), 3023–3033 (2021).
  • Chaib S , TchkoniaT, KirklandJL. Cellular senescence and senolytics: the path to the clinic. Nat. Med., 28(8), 1556–1568 (2022).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.