The emerging predictive and prognostic role of aggressive-variant-associated tumor suppressor genes across prostate cancer stages

Pedrani, Martino; Barizzi, Jessica; Salfi, Giuseppe; Nepote, Alessandro; Testi, Irene; Merler, Sara; Castelo-Branco, Luis; Pereira Mestre, Ricardo; Turco, Fabio; Tortola, Luigi; Theurillat, Jean-Philippe; Gillessen, Silke; Vogl, Ursula

doi:10.3390/ijms26010318

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Theurillat_2025_MDPI_ijms_The Emerging Predictive

Journal article

The emerging predictive and prognostic role of aggressive-variant-associated tumor suppressor genes across prostate cancer stages

Pedrani, Martino Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland - Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Italy
Barizzi, Jessica Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale (EOC), Locarno, Switzerland
Salfi, Giuseppe ORCID Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland - Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Nepote, Alessandro Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland - Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - AOU San Luigi Gonzaga, Department of Oncology, University of Torino, Italy
Testi, Irene Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland - Medical Oncology Unit, University Hospital of Parma, Italy
Merler, Sara ORCID Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland - Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Section of Innovation Biomedicine—Oncology Area, Department of Engineering for Innovation Medicine, University of Verona and Verona University Hospital Trust, Italy
Castelo-Branco, Luis Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
Pereira Mestre, Ricardo ORCID Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland - Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Turco, Fabio Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
Tortola, Luigi Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
Theurillat, Jean-Philippe ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Gillessen, Silke ORCID Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland - Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Vogl, Ursula Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland

2025

Published in:

International journal of molecular sciences. - 2025, vol. 26, no. 1, p. 318

Aggressive variant prostate cancer (AVPC)

English 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.

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