The androgen receptor malignancy shift in prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Androgens and the androgen receptor (AR) are crucial for normal prostate development and function.
• In prostate cancer, the AR shifts to support malignant cell proliferation and survival, a phenomenon termed the AR malignancy shift.

Purpose of the Study:

• To review current knowledge on the AR malignancy shift.
• To discuss its DNA-binding patterns, transcriptome changes, drivers, and clinical implications.

Main Methods:

• Review of existing literature on the AR malignancy shift.
• Analysis of DNA-binding patterns and transcriptome changes in benign vs. carcinoma cells.
• Examination of AR cistrome alterations in model systems.

Main Results:

• In prostate cancer, AR binding shifts from consensus sites to associate with motifs like FOXA1 and HOXB13.
• This altered AR cistrome drives transcription of genes promoting a malignant phenotype.
• Mutations in localized prostate cancer can induce AR cistrome changes, supporting the AR malignancy shift concept.

Conclusions:

• The AR malignancy shift is essential for prostate cancer cell transformation.
• Revising prostate cancer classification based on the AR malignancy shift may enhance outcome prediction and treatment.
• Targeting factors driving the AR malignancy shift could lead to novel therapeutic and preventive strategies.