Year: 2024
Type: article
Abstract: 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.
Institutions: University of Parma, City Of Hope National Medical Center, Beckman Research Institute, Consejo Superior de Investigaciones Científicas, Instituto de Parasitología y Biomedicina "López - Neyra", Institució Catalana de Recerca i Estudis Avançats, Universitat Autònoma de Barcelona, Centre de Recerca Matemàtica, Universidad de Granada
Language: English
Subfield: Modeling and Simulation
Field: Mathematics
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,290
Funders: Istituto Nazionale di Alta Matematica "Francesco Severi", Isaac Newton Institute for Mathematical Sciences, Centres de Recerca de Catalunya, European Commission, Generalitat de Catalunya, Ministerio de Economía y Competitividad, 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, Ministerio de Universidades, NextGenerationEU
Awards: G1072893519, G1092424111, G1186134865, G1269317468, G1333822313, G1401168639, G1575657597, G1650125035, G1670599692, G1686765077, G1849103467, G1855990336, G199520308, G1995558181, G2019402066, G2064873908, G2065685387, G2067457382, G2158560227, G2189360572, G219704740, G2262748287, G2309174360, G231133531, G2314889799, G2317340612, G2462415295, G252646220, G2633911021, G2660406951, G279363373, G3005324705, G3178914890, G318412399, G3348938521, G3407446885, G3480869486, G3518538256, G3546882995, G3681454997, G3691759950, G3720316055, G3825600141, G3946622174, G4027050006, G4042783231, G4045293325, G410571670, G4141536556, G4228227490, G425668148, G4303566950, G430777504, G451917667, G4844356218, G490430286, G4925834383, G4956596091, G4993905653, G5027649366, G5110933805, G5195188938, G523076202, G5245466801, G526084217, G5339074417, G5421974903, G5456286744, G5510928366, G5539308778, G5796505130, G5967599077, G5969143191, G5972032401, G6033112984, G6054710752, G617794351, G6298273575, G6307970414, G6325762137, G6384254145, G646276720, G6520718613, G6656126374, G6893394547, G7084143925, G7290105047, G7358581835, G7453477117, G7476827183, G7555275732, G787121397, G7880934544, G8443913929, G84477964, G8507684722, G8522095481, G8571576473, G8575141037, G8691980622, G8836758907, G8920660035, G972786147, G99296377
OpenAlex ID: W4403591807