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Updated: Nov 19, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Landscape of Cyclin Pathway Genomic Alterations Across 5,356 Prostate Cancers: Implications for Targeted Therapeutics

Denis L Jardim1, Sherri Z Millis2, Jeffrey S Ross2

  • 1Department of Clinical Oncology, Hospital Sirio Libanes, São Paulo, Brazil.

The Oncologist
|February 1, 2021
PubMed

Insights

Genomic alterations in the cyclin pathway occur in nearly 10% of prostate cancers, offering new therapeutic targets. These cyclin sensitizing alterations frequently co-occur with androgen receptor (AR) alterations, impacting treatment resistance.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The cyclin pathway plays a role in cell cycle regulation and is implicated in cancer development.
  • Understanding cyclin pathway alterations in prostate cancer is crucial for identifying resistance mechanisms and therapeutic opportunities.

Purpose of the Study:

  • To investigate the frequency and spectrum of genomic alterations in cyclin-related genes and their co-occurrence with androgen receptor (AR) alterations in prostate cancer.
  • To assess the potential of cyclin pathway abnormalities as therapeutic targets and markers of treatment resistance.

Main Methods:

  • Comprehensive genomic profiling using next-generation sequencing (315 genes) on 5,356 prostate cancer samples.
  • Analysis focused on cyclin-activating/sensitizing genes (e.g., CDK4, CCND1, CDKN2A/B), AR gene, and resistance-associated genes (RB1, CCNE1).

Main Results:

  • Genomic abnormalities in the cyclin sensitizing pathway were identified in 9.7% of tumors.
  • Frequent alterations included CCND1 amplification (4.2%) and CDKN2A/B loss (2.4% each).
  • Alterations in RB1 (9.7%) and CCNE1 (1.2%) were associated with therapeutic resistance, while AR alterations were found in 20.9% of cases. Cyclin sensitizing alterations were more common with AR alterations.

Conclusions:

  • Cyclin pathway genomic alterations are present in a significant subset of prostate cancers, representing potential therapeutic vulnerabilities.
  • The frequent co-occurrence of cyclin sensitizing alterations with AR alterations suggests complex interactions influencing treatment response and resistance in prostate cancer.

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