Supervisors info:
Θεοχάρης Σταμάτιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γακιοπούλου Χαρίκλεια, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Γιαννοπούλου Ιωάννα, ΕΔΙΠ, Ιατρική Σχολή, ΕΚΠΑ
Summary:
The dissertation explores the pivotal role of the Eph/ephrin system in breast cancer and its potential as a therapeutic target. The study begins by providing an overview of the Eph and ephrin family, discussing their structural characteristics and different signaling mechanisms, including ligand-dependent and ligand-independent signaling. The diverse functions of the Eph/ephrin system in neural and synaptic formation, tissue assembly, stem cell proliferation, immune system regulation, and homeostasis preservation are explored.
Furthermore, it delves into the implications of the Eph/ephrin system in cancer, focusing on its roles in promoting or suppressing tumor progression. It examines mechanisms such as neoangiogenesis, vascular mimicry, and angiogenesis under hypoxic conditions, along with its effects on the tumor microenvironment, tumor-infiltrating lymphocytes, cancer immunity and the connection of Eph receptors and ephrins with the process of epithelial- mesenchymal transition.
Further, the dissertation explores the specific implications of the Eph/ephrin system in breast cancer, considering its epidemiology, heterogeneous subtypes and its natural roles in mammary gland development. It provides an in-depth analysis of the roles of individual Eph receptors in breast cancer and proceeds to explore a diverse range of approaches for combating breast cancer by specifically targeting Eph receptors. These approaches encompass a comprehensive array of potential interventions such as antibodies that can selectively bind to Eph receptors and disrupt their signaling pathways. Additionally immunotherapy techniques are examined, which aim to harness the power of the immune system to recognize and eliminate breast cancer cells expressing Eph receptors. Other mechanisms include the design of small molecule inhibitors, which inhibit the kinase or the extracellular domain of the receptors as well as targeting epigenetic enzymes important for Eph expression and the development of peptides that interact with Eph receptors, either by blocking their activity or triggering their internalization, thereby impairing the growth and survival of breast cancer cells. More promising techniques include the use of conjugated peptides or antibodies and exosoms for targeted drug delivery, along with the use of natural product derivatives, miRNAs and lastly indirectly targeting Eph receptors due to their synthetic lethality or interaction with other molecules. These innovative targeting strategies hold great promise for advancing breast cancer treatment and augment moving closer to personalized therapies that can improve patient outcomes while minimizing the adverse effects on healthy tissues.
Keywords:
Eph receptors, Ephrins, Breast cancer, Targeted cancer strategies, Precision medicine
