Genetic and epigenetic features of neuroendocrine prostate cancer and their emerging applications

Xintong Zhang; Edward Barnett; Jim Smith; Emma Wilkinson; Rathan M Subramaniam; Amir Zarrabi; Euan J Rodger; Aniruddha Chatterjee

doi:10.1016/bs.ircmb.2023.06.002

Genetic and epigenetic features of neuroendocrine prostate cancer and their emerging applications

Int Rev Cell Mol Biol. 2024:383:41-66. doi: 10.1016/bs.ircmb.2023.06.002. Epub 2023 Jul 7.

Authors

Xintong Zhang¹, Edward Barnett¹, Jim Smith², Emma Wilkinson³, Rathan M Subramaniam⁴, Amir Zarrabi⁵, Euan J Rodger¹, Aniruddha Chatterjee⁶

Affiliations

¹ Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
² Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Te Whatu Ora/Health New Zealand, Wellington, New Zealand.
³ Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
⁴ Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Faculty of Medicine, Nursing, Midwifery and Health Sciences, The University of Notre Dame Australia, Fremantle, WA, Australia; Department of Radiology, Duke University, Durham, NC, United States.
⁵ Te Whatu Ora/Health New Zealand, Wellington, New Zealand; Precision Urology, Dunedin, New Zealand.
⁶ Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Honorary Professor, School of Health Sciences and Technology, UPES University, Dehradun, India. Electronic address: aniruddha.chatterjee@otago.ac.nz.

PMID: 38359970
DOI: 10.1016/bs.ircmb.2023.06.002

Abstract

Prostate cancer is the second most prevalent cancer in men globally. De novo neuroendocrine prostate cancer (NEPC) is uncommon at initial diagnosis, however, (treatment-induced) t-NEPC emerges in up to 25% of prostate adenocarcinoma (PRAD) cases treated with androgen deprivation, carrying a drastically poor prognosis. The transition from PRAD to t-NEPC is underpinned by several key genetic mutations; TP53, RB1, and MYCN are the main genes implicated, bearing similarities to other neuroendocrine tumours. A broad range of epigenetic alterations, such as aberrations in DNA methylation, histone post-translational modifications, and non-coding RNAs, may drive lineage plasticity from PRAD to t-NEPC. The clinical diagnosis of NEPC is hampered by a lack of accessible biomarkers; recent advances in liquid biopsy techniques assessing circulating tumour cells and ctDNA in NEPC suggest that the advent of non-invasive means of monitoring progression to NEPC is on the horizon. Such techniques are vital for NEPC management; diagnosis of t-NEPC is crucial for implementing effective treatment, and precision medicine will be integral to providing the best outcomes for patients.

Keywords: Epigenetics; Genetics; Neuroendocrine prostate cancer; Prostate cancer; Treatment.

MeSH terms

Androgen Antagonists
Epigenesis, Genetic
Humans
Male
Neuroendocrine Tumors* / genetics
Neuroendocrine Tumors* / pathology
Prostatic Neoplasms* / genetics
Prostatic Neoplasms* / pathology
Prostatic Neoplasms* / therapy

Substances

Androgen Antagonists