ABSTRACT
Purpose: The therapeutic decision for the management of breast cancer (BC) patients is based on the evaluation of prognostic factors alongside clinical and pathological parameters. Despite the use of standard biomarkers, response and resistance to therapy represent a challenge for clinicians. Among the new potential biomarkers for BC the ZNF217 gene have gained importance in recent years. However, while associations between ZNF217 gene copy number and clinicopathological characteristics have been established, its correlation with treatment response remains unclear. Patients and Methods: This study aimed to evaluate the ZNF217 gene copy number and establish its associations with treatment response in estrogen receptor positive (ERα+) and ERα negative (ERα-) BC cell lines. In addition, a validation of the relationship between ZNF217 gene copy number and its prognostic value was performed using datasets of BC patients retrieved from the cBioPortal public database. Results: Our data show that in ERα+ cells, ZNF217 gene copy number increase (amplification), while cell proliferation decreases in response to standard drug treatments. In contrast, both ZNF217 gene copy number (gain) and cell proliferation increases in response to standard drug treatments in ERα- cells. The results obtained align with findings from the cBioPortal database analysis, demonstrating that ERα+/HER2- low proliferation patients, exhibiting ZNF217 gene amplification or gain, have a significantly higher survival probability after treatment, compared to ERα-/HER2- and HER2+ patients. Conclusion: Our results suggest that in ERα+ BC cells, ZNF217 gene amplification could be indicative of a favorable response, while in ERα- BC cells, ZNF217 gene gain could be postulated as a potential predictor of treatment resistance. A broader understanding of the role of ZNF217 gene in treatment response, together with prospective studies in BC patients, could contribute to confirming our data, as well as optimizing existing treatments and exploring novel approaches to improve overall cancer treatment outcomes.
ABSTRACT
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.
ABSTRACT
Pesticides are a group of environmental pollutants widely used in agriculture to protect crops, and their indiscriminate use has led to a growing public awareness about the health hazards associated with exposure to these substances. In fact, exposure to pesticides has been associated with an increased risk of developing diseases, including cancer. In a study previously published by us, we observed the induction of specific chromosomal alterations and, in general, the deleterious effect of pesticides on the chromosomes of five individuals exposed to pesticides. Considering the importance of our previous findings and their implications in the identification of cytogenetic biomarkers for the monitoring of exposed populations, we decided to conduct a new study with a greater number of individuals exposed to pesticides. Considering the above, the aim of this study was to evaluate the type and frequency of chromosomal alterations, chromosomal variants, the level of chromosomal instability and the clonal heterogeneity in a group of thirty-four farmers occupationally exposed to pesticides in the town of Simijacá, Colombia, and in a control group of thirty-four unexposed individuals, by using Banding Cytogenetics and Molecular Cytogenetics (Fluorescence in situ hybridization). Our results showed that farmers exposed to pesticides had significantly increased frequencies of chromosomal alterations, chromosomal variants, chromosomal instability and clonal heterogeneity when compared with controls. Our results confirm the results previously reported by us, and indicate that occupational exposure to pesticides induces not only chromosomal instability but also clonal heterogeneity in the somatic cells of people exposed to pesticides. This study constitutes, to our knowledge, the first study that reports clonal heterogeneity associated with occupational exposure to pesticides. Chromosomal instability and clonal heterogeneity, in addition to reflecting the instability of the system, could predispose cells to acquire additional instability and, therefore, to an increased risk of developing diseases.
