Prostate cancer: pathogenesis
- Mechanism
Prostate cancer grows on androgens and builds on inherited risk, gene fusions and loss of tumour suppressors.
What it is
Prostatic adenocarcinoma is the commonest cancer of men in many countries and one of the leading causes of cancer death in men, including in Colombia. Its risk rises with age, with African ancestry and with family history. Androgens are needed for growth: the tumour depends on the androgen receptor, which is why androgen deprivation works and why resistance often involves receptor amplification or variants. Germline variants in BRCA2, BRCA1, ATM, HOXB13 and mismatch repair genes raise risk. About half of tumours carry fusions of the androgen-regulated TMPRSS2 gene to ETS transcription factors (ERG); PTEN loss activates PI3K-AKT signalling. High-grade prostatic intraepithelial neoplasia (PIN) is the precursor.
Step by step
- Inherited variants and age-related damage accumulate in luminal cells of the peripheral zone.
- Atypical cells fill existing ducts and acini: high-grade PIN.
- Androgen-receptor signalling drives a TMPRSS2-ERG fusion or other ETS rearrangement.
- PTEN loss and NKX3-1 loss promote growth and invasion; the basal layer disappears.
- Androgen deprivation shrinks the tumour, but clones that amplify or alter the androgen receptor escape.
- Castration-resistant clones metastasize, mainly to bone.
Clinical notes
- Men with BRCA2 variants have earlier and more aggressive prostate cancer and may benefit from PARP inhibitors.
- Screening with PSA is a shared decision because many detected cancers would never cause harm.
Test yourself
Think of the answer, then tap the question to see it.
What is the most common gene fusion in prostate cancer?
TMPRSS2-ERG, which puts an ETS transcription factor under androgen control.
Which inherited gene variant most clearly raises the risk of aggressive prostate cancer?
BRCA2 (HOXB13 also increases risk).
What distinguishes high-grade PIN from invasive carcinoma?
In PIN the atypical cells stay within pre-existing glands that keep their basal cell layer.
Elsewhere in DurgiPedia
- Translocations, amplifications and epigenetic changes in cancer
- Hereditary cancer syndromes: the table to know
- Nuclear receptors
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Prostate Cancer (StatPearls (NCBI Bookshelf), 2024).
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Representative model, for educational purposes only.