Emergence of cyclic hypoxia and the impact of PARP inhibitors on tumor progression
Tumor hypoxia is a dynamic phenomenon marked by fluctuations in oxygen levels across both rapid (seconds to minutes) and slow (hours to days) time scales. While short hypoxia cycles are relatively well understood, the mechanisms behind longer cycles remain largely unclear. In this paper, we present a novel mechanistic mathematical model that explains slow hypoxia cycles through feedback loops involving vascular expansion and regression, oxygen-regulated tumor growth, and toxic cytokine production. Our study reveals that, for the emergence of slow hypoxia cycles, endothelial cells must adapt by decreasing receptor activation as ligand concentration increases. Additionally, the interaction between tumor cells and toxic cytokines influences frequency and intensity of these cycles. By examining the effects of pharmacological interventions, specifically poly (ADP-ribose) polymerase inhibitors, we also demonstrate how targeting cell proliferation can help regulate oxygen levels. Our findings enhance the understanding of hypoxia regulation and suggest PARP proteins as promising therapeutic targets.
Authors
- Juan Soler (ORCID: https://orcid.org/0000-0002-8683-5994)
- F. Javier Oliver (ORCID: https://orcid.org/0000-0001-8468-1998)
- Martina Conte
- Tomás Alarcón (ORCID: https://orcid.org/0000-0002-8566-3676)
- Verónica Fernández (ORCID: https://orcid.org/0009-0008-4371-1431)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Autònoma de Barcelona (ES)
- University of Parma (IT)
- City Of Hope National Medical Center (US)
- Universidad de Granada (ES)
- Centre de Recerca Matemàtica (ES)
- Instituto de Parasitología y Biomedicina "López - Neyra" (ES)
Publication Details
- Journal
- npj Systems Biology and Applications
- Published
- 2024-10-22
- DOI
- https://doi.org/10.1038/s41540-024-00453-2
- Citations
- 3
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.85
Funders
- Istituto Nazionale di Alta Matematica "Francesco Severi"
- Isaac Newton Institute for Mathematical Sciences
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Ministerio de Ciencia e Innovación
- Junta de Andalucía
- Fundación Domingo Martínez
- Nature
- Gruppo Nazionale per la Fisica Matematica
- Engineering and Physical Sciences Research Council
- European Regional Development Fund
- Agencia Estatal de Investigación
- Division of Mathematical Sciences