Valeria Consoli
Ciclo: XXXVII ciclo-PON
Data inizio: 01/11/2021
Curriculum: Farmaceutico
Borsa: UNICT
Titolo tesi: Significance of Heme Oxygenase Modulation in Ferroptosis as a Novel Chemotherapeutic Strategy
Abstract: In the relentless battle against cancer, the pursuit of understanding and overcoming drug resistance remains at the forefront of medical research. Despite significant advancements in treatment protocols, the challenge of resistance to apoptosis-inducing drugs continues to thwart efforts to achieve long-term remission. Thus, the urge of finding valuable alternatives for patients in life-threatening conditions. In particular, this work delves into the intricate mechanisms of breast cancer biology, exploring novel pathways and potential therapeutic interventions. The core objective of this study is to investigate the role of iron homeostasis and oxidative stress in breast cancer progression. By focusing on the recently discovered process of ferroptosis, an iron-dependent form of cell death, this research aims to identify new drug candidates capable of circumventing drug resistance while elucidating the role of heme oxygenase (HO) system in breast cancer cells. Experimental plan includes the analysis of ferroptotic markers expression, reactive oxygen species (ROS) contribute, lipid peroxidation impact and iron metabolism involvement in different in vitro models in order to unveil HO role in ferroptosis and regulation of cellular fate. In the attempt to validate the theory of inducible isoform HO-1 being a potential marker for cells responsiveness to ferroptosis, it was possible to highlight the importance of its subcellular localization for understanding and predict cellular behaviour. The findings reveal a delicate balance between pro-oxidant and antioxidant conditions within cancer cells, with iron metabolism playing a pivotal role. The induction of ferroptosis by novel compounds, including natural compounds (curcumin and CAPE), newly synthetized derivatives and the off-label use of the antipsychotic drug haloperidol, was manageable to prove significant potential in reducing cell viability in different breast cancer cell lines. Notably, the study highlights the involvement of less-trodden pathways as ferritinophagy, offering new insights into the molecular routes that can be the subjects for further research in order to enhance treatment efficacy. As we journey through the complexities of breast cancer biology, this thesis not only sheds light on the underlying mechanisms of drug resistance but also paves the way for innovative therapeutic approaches. The exploration of ferroptosis as a valueble treatment strategy holds promise for improving outcomes and providing hope to patients facing the challenges of resistant breast cancer. In the pages that follow, we unravel the potential of targeting heme oxygenase system to rewrite the narrative of breast cancer therapy.
Tutor: Vanella
Data Conseguimento Titolo: 19/12/2024
Linkedin: https://www.linkedin.com/in/valeria-consoli-55581a1b6/
Email: valeria_consoli@yahoo.it
Periodi all'estero- Sede e data: IMDEA Alimentación - Madrid Institute for Advanced Studies in Food, Madrid, Spain (01/07/2022 - 31/12/2022)
Esperienze post-Dottorato ed attuale occupazione: Post-doc fellowship Fondazione Umberto Veronesi (a partire dal 1° febbraio 2025).