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Volume 26
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Anna Lisa Cammarota
1,
Albino Carrizzo
1,
Margot De Marco
1,
Nenad Bukvic
2,
Francesco Jacopo Romano
3,
Alessandra Rosati
1,* and
Massimiliano Chetta
4,5,*
1
Department of Medicine, Surgery and Dentistry “Schola Medica Salernitana”, University of Salerno, 84084 Baronissi, Italy
2
Medical Genetics Section, University Hospital Consortium Corporation Polyclinics of Bari, 70124 Bari, Italy
3
U.O.C. Oncology A.O.R.N., Cardarelli, 80131 Naples, Italy
4
U.O.C. Medical and Laboratory Genetics, A.O.R.N., Cardarelli, 80131 Naples, Italy
5
U.O.C. Anatomia Patologica, San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(20), 9933; https://doi.org/10.3390/ijms26209933 (registering DOI)
Submission received: 10 August 2025 / Revised: 27 September 2025 / Accepted: 10 October 2025 / Published: 12 October 2025
(This article belongs to the Special Issue Cell Proliferation and Differentiation in Cancer)
Review Reports Versions Notes

Abstract

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.
Keywords: transcription factors (TFs); dysregulation of TFs; in silico approach; molecular pathways transcription factors (TFs); dysregulation of TFs; in silico approach; molecular pathways

Share and Cite

MDPI and ACS Style

Cammarota, A.L.; Carrizzo, A.; De Marco, M.; Bukvic, N.; Romano, F.J.; Rosati, A.; Chetta, M. From Transcription Factors Dysregulation to Malignancy: In Silico Reconstruction of Cancer’s Foundational Drivers—The Eternity Triangle. Int. J. Mol. Sci. 2025, 26, 9933. https://doi.org/10.3390/ijms26209933

AMA Style

Cammarota AL, Carrizzo A, De Marco M, Bukvic N, Romano FJ, Rosati A, Chetta M. From Transcription Factors Dysregulation to Malignancy: In Silico Reconstruction of Cancer’s Foundational Drivers—The Eternity Triangle. International Journal of Molecular Sciences. 2025; 26(20):9933. https://doi.org/10.3390/ijms26209933

Chicago/Turabian Style

Cammarota, Anna Lisa, Albino Carrizzo, Margot De Marco, Nenad Bukvic, Francesco Jacopo Romano, Alessandra Rosati, and Massimiliano Chetta. 2025. "From Transcription Factors Dysregulation to Malignancy: In Silico Reconstruction of Cancer’s Foundational Drivers—The Eternity Triangle" International Journal of Molecular Sciences 26, no. 20: 9933. https://doi.org/10.3390/ijms26209933

APA Style

Cammarota, A. L., Carrizzo, A., De Marco, M., Bukvic, N., Romano, F. J., Rosati, A., & Chetta, M. (2025). From Transcription Factors Dysregulation to Malignancy: In Silico Reconstruction of Cancer’s Foundational Drivers—The Eternity Triangle. International Journal of Molecular Sciences, 26(20), 9933. https://doi.org/10.3390/ijms26209933

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