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Updated: Jan 4, 2026
Identification, Histological Characterization, and Dissection of Mouse Prostate Lobes for In Vitro 3D Spheroid Culture Models
Published on: September 18, 2018
From genomics to functions: preclinical mouse models for understanding oncogenic pathways in prostate cancer
Chuan Yu1, Kevin Hu1, Daniel Nguyen1
1Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, CA 95064, USA.
Abstract:
Next-generation sequencing has revealed numerous genomic alterations that induce aberrant signaling activities in prostate cancer (PCa). Among them are pathways affecting multiple cancer types, including the PI3K/AKT/mTOR, p53, Rb, Ras/Raf/MAPK, Myc, FGF, and Wnt signaling pathways, as well as ones that are prominent in PCa, including alterations in genes of AR signaling, the ETS family, NKX3.1, and SPOP. Cross talk among the oncogenic pathways can confer PCa resistance to therapy, particularly in advanced tumors, which are castration-resistant or show neuroendocrine features. Various experimental models, such as cancer cell lines, animal models, and patient-derived xenografts and organoids have been utilized to dissect PCa progression mechanisms. Here, we review the current preclinical mouse models for studying the most commonly altered pathways in PCa, with an emphasis on their interplays. We highlight the power of genetically engineered mouse models (GEMMs) in translating genomic discoveries into understanding of the functions of these oncogenic events in vivo. Developing and analyzing PCa mouse models will undoubtedly continue to offer new insights into tumor biology and guide novel rationalized therapy.
Insights
Genetically engineered mouse models (GEMMs) are crucial for understanding prostate cancer (PCa) progression and therapeutic resistance by dissecting aberrant signaling pathways and their interactions in vivo.
Area of Science:
- Oncology
- Genetics
- Cancer Biology
Background:
- Next-generation sequencing identifies numerous genomic alterations driving aberrant signaling in prostate cancer (PCa).
- Key pathways involved include PI3K/AKT/mTOR, p53, Rb, Ras/Raf/MAPK, Myc, FGF, Wnt, AR signaling, ETS family, NKX3.1, and SPOP.
- Pathway crosstalk contributes to therapeutic resistance in advanced, castration-resistant, or neuroendocrine prostate cancer.
Purpose of the Study:
- To review preclinical mouse models for studying commonly altered pathways in PCa.
- To emphasize the interplays among these oncogenic pathways.
- To highlight the utility of genetically engineered mouse models (GEMMs) in understanding PCa biology.
Main Methods:
- Review of current literature on preclinical mouse models for PCa research.
- Focus on genetically engineered mouse models (GEMMs).
- Analysis of how these models elucidate the in vivo functions of oncogenic events.
Main Results:
- GEMMs effectively translate genomic discoveries into functional insights.
- These models allow for the study of complex pathway interplays in vivo.
- GEMMs are powerful tools for dissecting PCa progression mechanisms.
Conclusions:
- Preclinical mouse models, particularly GEMMs, are essential for advancing prostate cancer research.
- Understanding pathway interplays is critical for overcoming therapeutic resistance.
- Continued development and analysis of PCa mouse models will drive novel therapeutic strategies.
