Aggressive variant prostate cancer (AVPC) is characterized by a molecular signature involving combined defects in TP53, RB1, and/or PTEN (AVPC-TSGs), identifiable through immunohistochemistry or genomic analysis. The reported prevalence of AVPC-TSG alterations varies widely, reflecting differences in assay sensitivity, treatment pressure, and disease stage evolution. Although robust clinical evidence is still emerging, the study of AVPC-TSG alterations in prostate cancer (PCa) is promising. Alterations in TP53, RB1, and PTEN, as well as the combined loss of AVPC-TSGs, may have significant implications for prognosis and treatment. These biomarkers might help predict responses to various therapies, including hormonal treatments, cytotoxic agents, radiotherapy, and targeted therapies. Understanding the impact of these molecular alterations in patients with PCa is crucial for personalized management. In this review, we provide a comprehensive overview of the emerging prognostic and predictive roles of AVPC-TSG alterations across PCa stages. Moreover, we discuss the implications of different methods used for detecting AVPC-TSG alterations and summarize factors influencing their prevalence. As our comprehension of the genomic landscape of PCa disease deepens, incorporating genomic profiling into clinical decision making will become increasingly important for improving patient outcomes.
International journal of molecular sciences. 2025 Jan 01*** epublish ***
Martino Pedrani, Jessica Barizzi, Giuseppe Salfi, Alessandro Nepote, Irene Testi, Sara Merler, Luis Castelo-Branco, Ricardo Pereira Mestre, Fabio Turco, Luigi Tortola, Jean-Philippe Theurillat, Silke Gillessen, Ursula Vogl
Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), 6500 Bellinzona, Switzerland., Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale (EOC), 6600 Locarno, Switzerland., Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.