Baseline CRPC — Androgen Deprivation Isn't Enough
Testes are silenced, but the tumor keeps growing on leftover androgen. This 3D companion renders the same supply-side (CYP17) vs receptor-side (AR) blockade mechanism as a real spatial pathway — source cell, enzyme checkpoint, and receptor cell laid out along one axis in three dimensions, orbited freely with drag and scroll.
- ~95% cut: Testicular testosterone (via ADT / orchiectomy)
- DHEA, ASD: Adrenal androgen source (converted intratumorally)
- Active: Intratumoral synthesis (tumor makes its own fuel)
- ~18–24 mo: CRPC onset (median after ADT start)
Why castration alone fails
Adrenal glands and tumor cells keep producing androgen precursors.
Residual androgen signaling
Small amounts of androgen are enough to keep AR active.
Clinical implication
Need drugs that hit the residual pathway directly.
Residual androgen keeps CRPC alive even after castration.
Abiraterone — Shutting Down CYP17 at the Source
Blocks the enzyme that makes androgen, before it ever forms — rendered here as a 3D checkpoint node that molecules bounce off when the drug is active.
- CYP17A1: Target enzyme (17α-hydroxylase / C17,20-lyase)
- Adrenal + tumor: Synthesis site blocked (both sources hit)
- + prednisone: Co-administered (offsets mineralocorticoid excess)
- 1000 mg/day: Typical dose (oral, once daily)
CYP17 enzyme role
Converts cholesterol precursors into androgen building blocks.
Upstream shutdown
No enzyme activity means no new androgen molecules form.
Downstream effect
Receptor has nothing left to bind.
Supply cut off before synthesis — molecules never reach the receptor cell.
Enzalutamide — Blocking the Androgen Receptor Directly
Androgen still forms and travels the full 3D path to the tumor cell, but can no longer dock at the receptor.
- Androgen receptor: Target (competitive antagonist)
- Blocked: Nuclear translocation (AR can't enter nucleus)
- Blocked: DNA binding (no transcriptional activity)
- 160 mg/day: Typical dose (oral, once daily)
AR antagonism
Occupies the receptor's binding pocket, blocking androgen.
Downstream consequences
No nuclear translocation, no gene transcription.
Contrast with abiraterone
Production continues; only signaling is stopped.
Receptor blocked regardless of upstream supply.
Supply vs Receptor — Two Ways to Stop the Same Signal
Same goal, two blockade points along one pathway — pick either drug and watch which checkpoint lights up red.
- CYP17 (supply): Abiraterone target (upstream enzyme)
- AR (receptor): Enzalutamide target (downstream signaling)
- Low AR activity: Shared endpoint (via different routes)
- Partial: Cross-resistance (some tumors escape either)
Pathway position
One acts upstream, the other acts at the receptor.
Complementary logic
Blocking both points narrows the tumor's escape routes.
Sequencing considerations
Order and combination affect resistance patterns.
Mechanisms complement, not duplicate, one another.
Convergent Suppression of Residual Androgen Signaling
Both drugs land at the same place: minimal AR activity — both checkpoints blocked at once in this final stage.
- Low: Net AR signaling (via either mechanism)
- Common: Sequential use (switch on progression)
- Ongoing: Combination trials (with chemo, PARP, etc.)
- Established: Survival benefit (vs. ADT alone in CRPC)
Convergent efficacy
Different blockade points, same suppressed-signaling outcome.
Sequencing and combination
Often used one after another or alongside other agents.
Clinical takeaway
Complementary mechanisms broaden treatment options.
Two paths, one durable suppression.