Journal Article (Review Article)

DKFZ-2024-01458

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Intercellular pathways of cancer treatment-related cardiotoxicity and their therapeutic implications: the paradigm of radiotherapy.

Logotheti, S. (First author)DKFZ* ; Pavlopoulou, A. ; Rudsari, H. K. ; Galow, A.-M. ; Kafalı, Y. ; Kyrodimos, E. ; Giotakis, A. I. ; Marquardt, S. ; Velalopoulou, A. ; Verginadis, I. I. ; Koumenis, C. ; Stiewe, T. ; Zoidakis, J. ; Balasingham, I. ; David, R. ; Georgakilas, A. G.

2024
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.pharmthera.2024.108670

Abstract: Advances in cancer therapeutics have improved patient survival rates. However, cancer survivors may suffer from adverse events either at the time of therapy or later in life. Cardiovascular diseases (CVD) represent a clinically important, but mechanistically understudied complication, which interfere with the continuation of best-possible care, induce life-threatening risks, and/or lead to long-term morbidity. These concerns are exacerbated by the fact that targeted therapies and immunotherapies are frequently combined with radiotherapy, which induces durable inflammatory and immunogenic responses, thereby providing a fertile ground for the development of CVDs. Stressed and dying irradiated cells produce 'danger' signals including, but not limited to, major histocompatibility complexes, cell-adhesion molecules, proinflammatory cytokines, and damage-associated molecular patterns. These factors activate intercellular signaling pathways which have potentially detrimental effects on the heart tissue homeostasis. Herein, we present the clinical crosstalk between cancer and heart diseases, describe how it is potentiated by cancer therapies, and highlight the multifactorial nature of the underlying mechanisms. We particularly focus on radiotherapy, as a case known to often induce cardiovascular complications even decades after treatment. We provide evidence that the secretome of irradiated tumors entails factors that exert systemic, remote effects on the cardiac tissue, potentially predisposing it to CVDs. We suggest how diverse disciplines can utilize pertinent state-of-the-art methods in feasible experimental workflows, to shed light on the molecular mechanisms of radiotherapy-related cardiotoxicity at the organismal level and untangle the desirable immunogenic properties of cancer therapies from their detrimental effects on heart tissue. Results of such highly collaborative efforts hold promise to be translated to next-generation regimens that maximize tumor control, minimize cardiovascular complications, and support quality of life in cancer survivors.

Keyword(s): Big data ; Cancer ; Cancer therapy ; Cardiooncology ; Cardiovascular diseases ; Intercellular pathways ; Multidisciplinary research ; Multimodal omics ; Radiotherapy ; Radiotherapy-induced CVDs ; Systems medicine

Note: #EA:E041# / Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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Contributing Institute(s):

1. Med. Physik in der Radioonkologie (E041)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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