Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May;3(5):e742.
doi: 10.1002/cpz1.742.

Preclinical Models of Neuroendocrine Prostate Cancer

Alessia Cacciatore  1 , Domenico Albino  1 , Carlo V Catapano  1 , Giuseppina M Carbone  1
Affiliations
Review

Preclinical Models of Neuroendocrine Prostate Cancer

Alessia Cacciatore et al. Curr Protoc. 2023 May.

Abstract

Prostate cancer (PCa) is the most common malignancy and the second leading cause of cancer-related death amongst men in the United States. Neuroendocrine prostate cancer (NEPC) can either arise de novo or emerge as a consequence of therapy. De novo NEPC is rare, with an incidence of <2% of all PCa cases. In contrast, treatment-induced NEPC is frequent with >20% of patients with metastatic castration-resistant prostate cancer (CRPC) reported to progress to neuroendocrine (NE) differentiation. The emergence of treatment-induced NEPC is linked to the increased therapeutic pressure, due to the broad application of androgen deprivation therapy (ADT) for PCa management and the development of novel more potent androgen receptor (AR) pathway inhibitors. NEPC is a high-grade tumor type characterized by aggressive phenotype and clinical behavior. Patients affected by NEPC frequently develop visceral metastases and have a poor prognosis. The molecular mechanisms underlying the development and progression of NEPC are still poorly understood. Transcriptional and epigenetic reprogramming appears to be involved in NE progression. In this review, we aim to provide a comprehensive view of the available models for NEPC detailing their strengths and limitations. Moreover, we describe novel approaches to expand the repertoire of preclinical models to better study, prevent, or reverse NEPC. The integration of multiple preclinical models along with molecular and omics approaches will provide important insights to understand disease progression and to devise novel therapeutic strategies for the management of NEPC in the near future. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation of organoids starting from the prostate gland of a GEMM or a human PDX Basic Protocol 2: Ex vivo tumor sphere formation.

Keywords: genetically engineered mouse model (GEMM); neuroendocrine prostate cancer (NEPC); patient-derived xenografts (PDX); preclinical models.

PubMed Disclaimer

References

Literature Cited

    1. Aggarwal, R., Huang, J., Alumkal, J. J., Zhang, L., Feng, F. Y., Thomas, G. V., Weinstein, A. S., Friedl, V., Zhang, C., Witte, O. N., Lloyd, P., Gleave, M., Evans, C. P., Youngren, J., Beer, T. M., Rettig, M., Wong, C. K., True, L., Foye, A., … Small, E. J. (2018). Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: A multi-institutional prospective study. Journal of Clinical Oncology, 36(24), 2492-2503. https://doi.org/10.1200/JCO.2017.77.6880
    1. Albino, D., Falcione, M., Uboldi, V., Temilola, D. O., Sandrini, G., Merulla, J., Civenni, G., Kokanovic, A., Stürchler, A., Shinde, D., Garofalo, M., Mestre, R. P., Constâncio, V., Wium, M., Burrello, J., Baranzini, N., Grimaldi, A., Theurillat, J.- P., Bossi, D., … Carbone, G. M. (2021). Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer. Communications Biology, 4(1), 119. https://doi.org/10.1038/s42003-020-01642-5
    1. Beltran, H., Prandi, D., Mosquera, J. M., Benelli, M., Puca, L., Cyrta, J., Marotz, C., Giannopoulou, E., Chakravarthi, B. V. S. K., Varambally, S., Tomlins, S. A., Nanus, D. M., Tagawa, S. T., Van Allen, E. M., Elemento, O., Sboner, A., Garraway, L. A., Rubin, M. A., & Demichelis, F. (2016). Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nature Medicine, 22(3), 298-305. https://doi.org/10.1038/nm.4045
    1. Beltran, H., Rickman, D. S., Park, K., Chae, S. S., Sboner, A., Macdonald, T. Y., Wang, Y., Sheikh, K. L., Terry, S., Tagawa, S. T., Dhir, R., Nelson, J. B., De La Taille, A., Allory, Y., Gerstein, M. B., Perner, S., Pienta, K. J., Chinnaiyan, A. M., Wang, Y., … Rubin, M. A. (2011). Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discovery, 1(6), 487-495. https://doi.org/10.1158/2159-8290.CD-11-0130
    1. Beltran, H., Romanel, A., Conteduca, V., Casiraghi, N., Sigouros, M., Franceschini, G. M., Orlando, F., Fedrizzi, T., Ku, S.-Y., Dann, E., Alonso, A., Mosquera, J. M., Sboner, A., Xiang, J., Elemento, O., Nanus, D. M., Tagawa, S. T., Benelli, M., & Demichelis, F. (2020). Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer. Journal of Clinical Investigation, 130(4), 1653-1668. https://doi.org/10.1172/JCI131041

MeSH terms

Substances

LinkOut - more resources