Breast Cancer: Targets and Therapy (Mar 2023)
Chromosomal Instability as Enabling Feature and Central Hallmark of Breast Cancer
Abstract
Giovanny Castellanos,1,2 Duván Sebastián Valbuena,2 Erika Pérez,2 Victoria E Villegas,3 Milena Rondón-Lagos2 1Maestría en Ciencias Biológicas, Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia; 2School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia; 3Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, ColombiaCorrespondence: Milena Rondón-Lagos, Tunja, 150003, Colombia, Tel +57 608 7428263, Fax +57 608 7405626, Email [email protected]: Chromosomal instability (CIN) has become a topic of great interest in recent years, not only for its implications in cancer diagnosis and prognosis but also for its role as an enabling feature and central hallmark of cancer. CIN describes cell-to-cell variation in the number or structure of chromosomes in a tumor population. Although extensive research in recent decades has identified some associations between CIN with response to therapy, specific associations with other hallmarks of cancer have not been fully evidenced. Such associations place CIN as an enabling feature of the other hallmarks of cancer and highlight the importance of deepening its knowledge to improve the outcome in cancer. In addition, studies conducted to date have shown paradoxical findings about the implications of CIN for therapeutic response, with some studies showing associations between high CIN and better therapeutic response, and others showing the opposite: associations between high CIN and therapeutic resistance. This evidences the complex relationships between CIN with the prognosis and response to treatment in cancer. Considering the above, this review focuses on recent studies on the role of CIN in cancer, the cellular mechanisms leading to CIN, its relationship with other hallmarks of cancer, and the emerging therapeutic approaches that are being developed to target such instability, with a primary focus on breast cancer. Further understanding of the complexity of CIN and its association with other hallmarks of cancer could provide a better understanding of the cellular and molecular mechanisms involved in prognosis and response to treatment in cancer and potentially lead to new drug targets.Keywords: breast cancer, genomic instability, chromosomal instability, clonal heterogeneity, resistance to therapy, therapeutic targets
