Twenty-five papers, two collections , one coherent argument .

Mutations Provide Potential, but Environment Determines Expression

Autopsy pathology. The foundational paradox establishing why terrain matters.

Metabolism, Epigenetics, and Lineage Plasticity

How metabolic state governs cellular identity and evolutionary trajectory.

Tumour Ecology and Evolutionary Stability

The ecological model of tumour progression. Why stability is actively maintained, and what its collapse enables.

Cancer as an Ecological and Evolutionary System

The capstone paper. Gatenby, Aktipis, and Zhang on why ecological management outperforms elimination, with clinical trial validation.

PSA Kinetics and the Natural History of Prostate Cancer

Decades of natural history data, Johansson, Albertsen, PIVOT, ProtecT, establishing that biological constraint is the default state of most localised prostate cancer.

The Primer

Full technical paper. Containment, evolution, and the ecology of indolent prostate cancer.

Chronic Activation vs Oscillation

Why pulsatile and chronic signalling produce different cellular outcomes.

mTOR as Integrative Hub

mTOR as multi-signal integrator. Why rhythm loss is the precise mechanism of harm.

MDM2 as Convergence Point

One upstream cause, two converging failures. The central mechanistic argument.

Rapamycin, mTOR Oscillation, and the p53-MDM2 Axis

Full mechanism linking mTOR suppression to p53 functional restoration.

Testosterone, p53, and the MDM2 System

The saturation model. Why physiological TRT differs from supraphysiological exposure.

Sirtuins, NAD⁺, and the Quiet Biology Framework

Acetylation as a second parallel control layer alongside phosphorylation.

The Three Layers of Intervention

Output, signalling, and structural layers. Why durability requires acting across all three.

Signal, Stress, and Selection

The four-signal temporal architecture. Why sequencing matters more than activation strength.

Dynamic Fitness Landscapes and Evolutionary Constraint in Prostate Cancer

Why oscillating environments prevent tumour populations from reaching stable adaptive optima. The evolutionary mechanism underlying the protocol's design.

From Intervention to Environment

The protocol's operational logic. Signal clarity as the central design principle.

Mitophagy and Mitochondrial Quality Control

The PINK1/Parkin pathway. Why mitochondrial quality is the cellular foundation of the structural layer.

Retatrutide as Metabolic Field Maintenance

Triple agonism. Systemic metabolic field restoration as structural foundation.

Pioglitazone at Low Dose

PPAR-γ activation. Cumulative stromal remodelling at 7.5mg.

Doxycycline: Multi-Pillar Analysis

Full four-pillar convergence: MMP, CSC mitochondria, NF-κB -> p53, intraprostatic microbiome.

Oestrogen's Role in Prostate Cancer

Four-mechanism analysis. ERα/ERβ balance, intratumoral aromatase, estrobolome, xenoestrogens.

Bipolar Androgen Therapy: Clinical Validation

BAT mechanism. Oscillation principle applied to CRPC. PSA50 77-94%.

A Hierarchy of Biological Signals

Five levels from field conditions to clinical outcome. The architectural frame for the whole series.

B7-H3 as an Adaptive Surface Phenotype

Checkpoint expression as a state marker of androgen suppression, inflammatory tone, and microenvironmental pressure. Why standard-of-care treatment actively upregulates the target it is now being combined with therapies to address.

Exercise as Medicine

Mechanistic justification and clinical application of exercise across androgen deprivation, ARPI, and chemotherapy. Three independent and additive mechanistic legs: AMPK/mTOR metabolic signalling, mitochondrial quality control, and stromal remodelling via the CNTF axis.

When Cleanup Becomes Advantage

Mitophagy as adaptive mechanism in cancer. Why single-pathway thinking fails and why oscillating perturbation models remain valid.

Mitochondrial Quality Control as a State-Determining Axis

The p53–MDM2–mitophagy circuit as a governor of cellular phenotypic identity. How mitochondrial quality determines which cellular states are epigenetically accessible.

L₁ Terrain

The biological ground the tumour grows in — metabolic, hormonal, inflammatory. Most relevant at Phases 01–03.

Finley Proudfoot, 2026

L₂ Signal

Tumour behaviour depends on the inputs the system receives. Changing the signal changes the trajectory. Most relevant at Phases 03–05.

Finley Proudfoot, 2026

L₃ Selection

Chronic intervention selects for resistance — oscillating intervention does not. Timing is itself a therapeutic variable. Most relevant at Phases 04–05.

Finley Proudfoot, 2026