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Immunogenomic profiles associated with response to life-prolonging agents in prostate cancer

British Journal of Cancer volume 129, pages 1050–1060 (2023)Cite this article

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Abstract

Prostate cancer is the most commonly diagnosed cancer but the management of advanced prostate cancer remains a therapeutic challenge, despite the survival benefits imparted by several therapeutic discoveries targeting different molecular pathways. The mechanisms of resistance to androgen deprivation and tumour progression to lethal metastatic variants are often regulated by androgen receptor (AR) bypass mechanisms and/or neuroendocrine differentiation. Moreover, recent data also suggested the involvement of adaptive and innate infiltrated immune cells in prostate tumour progression. Improvements in cancer genome analyses contributed to a better understanding of antitumour immunity and provided solutions for targeting highly cancer-specific neoantigens generated from somatic mutations in individual patients. In this review, we investigated the current knowledge on the interplay between cancer development and the complex mechanisms of immune regulation. Particularly, we focused on the role of tumour immune microenvironment, generally characterised by strong barriers for immunotherapy, and we discuss the rationale for the potential application of single agent and combination immune-targeting strategies that could lead to improved outcomes. Careful selection based on clinical and genomic factors may allow identification of patients who could benefit from this treatment approach in multiple settings (from localised to advanced prostate tumour) and in different histological subtypes (from adenocarcinoma to neuroendocrine prostate cancer).

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Fig. 1: The effects of androgen-signalling on prostate cancer immune environment.
Fig. 2: The interplay between androgen receptor signalling, DNA damage and repair pathways and immune response and the related therapeutic targets in prostate cancer.

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Data sharing is not applicable to this article, as no data sets were generated or analysed during this study.

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Authors and Affiliations

  1. Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, 71122, Foggia, Italy

    Vincenza Conteduca

  2. IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014, Meldola, Italy

    Nicole Brighi, Giuseppe Schepisi & Ugo De Giorgi

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  1. Vincenza Conteduca
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  2. Nicole Brighi
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  3. Giuseppe Schepisi
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  4. Ugo De Giorgi
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All authors contributed to the conception and design of the review. VC, NB and GS drafted the manuscript. NB prepared the figures of the manuscript. UDG revised the manuscript. All authors approved the final version.

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Correspondence to Vincenza Conteduca.

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Competing interests

VC has served as a consultant/advisory board member for Janssen, Astellas, Merck, AstraZeneca, Amgen, EISAI, Recordati and Bayer and has received speaker honoraria or travel support from Astellas, Janssen, Ipsen, Bayer, Gilead and BristolMyers Squibb. UDG reports research support from AstraZeneca, Roche and Sanofi; and consultancy fees from Astellas, Bayer, BristolMyers Squibb, Ipsen, Janssen, Merck, Pfizer and Sanofi. No potential conflicts of interest were disclosed by the other authors.

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Conteduca, V., Brighi, N., Schepisi, G. et al. Immunogenomic profiles associated with response to life-prolonging agents in prostate cancer. Br J Cancer 129, 1050–1060 (2023). https://doi.org/10.1038/s41416-023-02354-3

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  • DOI: https://doi.org/10.1038/s41416-023-02354-3

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