From Transcription Factors Dysregulation to Malignancy: In Silico Reconstruction of Cancer’s Foundational Drivers—The Eternity Triangle

Cancer is a multifaceted disease characterized by uncontrolled cell division resulting from substantial disruptions of normal biological processes. Central to its development is cellular transformation, which involves a dynamic sequence of events including chromosomal translocations, genetic mutations, abnormal DNA methylation, post-translational protein modifications, and other genetic and epigenetic alterations. These changes compromise physiological regulatory mechanisms and contribute to accelerated tumor growth. A critical factor in this process is the dysregulation of transcription factors (TFs) which regulate gene expression and DNA transcription. Dysregulation of TFs initiates a cascade of biochemical events, such as abnormal DNA replication, that further enhance cell proliferation and increase genomic instability. This microenvironment not only sustains tumor growth but also promotes the accumulation of somatic mutations, thereby fueling tumor evolution and heterogeneity. In this study, we employed an in silico approach to identify TFs regulating 622 key genes whose mutations are implicated in carcinogenesis. Transcriptional regulatory networks were analyzed through bioinformatics methods to elucidate molecular pathways involved in cancer development. A thorough understanding of these processes may help to clarify the function of dysregulated TFs and facilitate the development of novel therapeutic approaches designed to make cancer treatments personalized and efficacious.