Prostate cancer

Clinical / Scientific

Prostate adenocarcinoma is typically androgen- dependent. Genomic drivers include AR, ETS fusions, PTEN/, DNA-repair defects and later lineage plasticity to neuroendocrine disease. Metabolic rewiring includes lipogenesis.

Molecular / histological subtypes

Core Biological Drivers

Androgen receptor

Lineage factor.

PTEN / PI3K

Common suppressor loss.

ETS fusions

TMPRSS2-ERG in many acinar tumours.

HRD / BRCA

Subset with PARP relevance.

Key Pathways

Androgen receptor

Scientific explanation

AR is a nuclear factor required for most prostate adenocarcinoma growth. Resistance can occur through AR amplification, splice variants, or lineage plasticity.

PI3K/AKT

Scientific explanation

phosphorylates PIP2 to PIP3, recruiting . supports growth, survival, glucose uptake and mTORC1 input. Pathway activation is common via PIK3CA mutation, PTEN loss or -tyrosine- signalling.

mTOR

Scientific explanation

mTORC1 integrates growth-factor and nutrient signals to drive protein synthesis, lipid synthesis and suppression. It sits downstream of PI3K/AKT and amino-acid sensing.

PARP / DNA repair

Scientific explanation

Homologous-recombination defects (BRCA1/2 and related) create dependence on PARP-mediated repair. Mismatch-repair deficiency creates hypermutation and immune visibility.

Wnt/β-catenin

Scientific explanation

Canonical Wnt signalling stabilizes β-catenin, driving TCF/LEF . APC loss is a classic colorectal initiating event; the pathway also contributes to stemness in several tissues.

Glycolysis

Scientific explanation

Aerobic (Warburg metabolism) supports ATP, biomass and redox buffering even when oxygen is available. Hexokinase, PKM2 and lactate export are frequent nodes.

Fatty-acid metabolism

Scientific explanation

De novo lipogenesis, fatty-acid oxidation and lipid uptake are rewired in a tumour-type-specific way, especially in hypoxic, obese-host, or OXPHOS-dependent subsets.

VEGF

Scientific explanation

family ligands drive endothelial sprouting and vascular permeability, a canonical tumour axis.

EMT

Scientific explanation

Epithelial–mesenchymal plasticity, driven by TWIST/SNAIL/ZEB and TGF-β/Wnt/Notch inputs, reduces adhesion and increases motility and stem-like features.

Pathway Convergence

Target → pathway → downstream effect → biological consequence. Shared intersections are mechanistic maps, not protocols.

Growth-factor signalling

Ligand or mutation-driven RTK input feeds PI3K/AKT and mTORC1, supporting anabolic growth. This is a map of signalling, not a treatment protocol.

Receptor tyrosine kinase
↓
PI3K/AKT
↓
mTOR
↓
Protein synthesis / growth

Energy stress

Energetic stress activates AMPK, which can restrain mTORC1. Biguanides and related tools map onto this axis in models.

Complex I / ATP stress
↓
AMPK
↓
mTOR restraint
↓
Reduced anabolism

Hypoxia to vessels

Low oxygen stabilizes HIF-1α, inducing VEGF and endothelial sprouting. Anti-angiogenic pharmacology intersects this axis but does not erase the tumour ecosystem.

Hypoxia
↓
HIF-1α
↓
VEGF
↓
Angiogenesis

Metabolic Vulnerabilities

Aerobic supports ATP, biomass and acidification even when oxygen is available. Extent varies by tumour and remains a vulnerability hypothesis rather than a uniform target.

De novo lipogenesis is AR-linked in many models.

Tumor Microenvironment

Disordered vasculature creates , HIF-1α stabilization, induction and immune-suppressive adenosine/lactate milieus.

Tumour-associated macrophages and myeloid-derived suppressor cells secrete cytokines that support invasion and blunt cytotoxic T cells.

Metastasis Module

Bone tropism dominates: osteoblastic niches, adhesion and chemokine axes.

Resistance Biology

AR amplification/splice variants, bypass RTKs, and neuroendocrine transdifferentiation.

Cancer Stemness

Wnt, Notch, Hedgehog, ALDH and CD44-associated programmes can mark stem-like fractions with quiescence and therapy tolerance. These markers are not interchangeable across tumour types.

Mechanism-Based Adjunctive Strategies

Compounds appear only where a mechanistic overlap exists for this cancer. Evidence tiers are not equivalent. Nothing here is a treatment recommendation.

Metformin

Clinical / Human EvidenceIn VivoIn VitroMechanistically Plausible

Target / Mechanism

Modest complex I inhibition raises AMP:ATP, activating and restraining hepatic and -linked anabolism. Direct antineoplastic efficacy is not established from that pharmacology alone.

Cancer relevance

activation and restraint provide a metabolic rationale in - and -linked tumours. Human data are mixed and do not establish metformin as cancer therapy.

Metabolic adjunctive research context. Convergence: AMPK, mTOR, Glycolysis.

Statins (HMG-CoA reductase inhibitors)

Clinical / Human EvidenceIn VitroMechanistically Plausible

Target / Mechanism

Inhibit HMG-CoA reductase, depleting mevalonate-pathway isoprenoids needed for RAS/RHO prenylation and some sterol-dependent growth programmes. Observational oncology signals are mixed and not a licence to treat cancer with statins.

Cancer relevance

Mevalonate-pathway blockade can affect prenylation of RAS-family GTPases. Observational human signals are mixed and confounding is substantial.

Mevalonate / prenylation mechanistic overlap. Convergence: RAS/RAF, Fatty-acid metabolism.

Itraconazole

Early ClinicalIn VivoIn Vitro

Target / Mechanism

Azole antifungal; off-target reports include Hedgehog-pathway antagonism and anti-angiogenic endothelial effects in experimental and early clinical settings. Not a licensed antineoplastic.

Cancer relevance

Hedgehog antagonism and anti-angiogenic endothelial reports exist, including early clinical probes. Not a licensed antineoplastic.

Hedgehog / angiogenesis research. Convergence: Hedgehog, Angiogenesis.

Niclosamide

In VitroIn VivoMechanistically Plausible

Target / Mechanism

uncoupler in cestodes; mammalian models report , Wnt/β-catenin and modulation. Those host-signalling findings are investigational/preclinical.

Cancer relevance

Models report Wnt/β-catenin, and effects. Host signalling findings remain investigational.

Wnt / STAT3 signalling models. Convergence: Wnt/β-catenin, JAK/STAT, mTOR.

Mebendazole

In VitroIn VivoMechanistically Plausible

Target / Mechanism

Benzimidazole that binds β-. Mammalian disruption, mitotic arrest and related signalling in cancer models are preclinical and are not an approved anticancer use.

Cancer relevance

disruption can trigger mitotic stress and in cell and animal models. This is not an established oncology use.

Experimental antimitotic / microtubule stress. Convergence: Apoptosis, p53.

Curcumin

In VitroMechanistically Plausible

Target / Mechanism

Polyphenol with promiscuous in-vitro NF-κB, and ROS effects. Bioavailability is poor; dish activity does not establish clinical anticancer efficacy.

Cancer relevance

In-vitro NF-κB/ effects are frequent. Poor bioavailability and absence of robust clinical anticancer efficacy keep this pathway-level.

Inflammatory-signalling dish models. Convergence: NF-κB, JAK/STAT.

Celecoxib

Clinical / Human EvidenceIn VivoIn Vitro

Target / Mechanism

Selective -2 reducing PGE2. Relevant to -associated epithelial neoplasia; cardiovascular risk and lack of broad anticancer approval constrain interpretation.

Cancer relevance

-2/PGE2 biology is relevant in some epithelial neoplasias. Cardiovascular risk and lack of broad anticancer approval apply. Do not equate polyp or biomarker studies with tumour cure.

Inflammation-associated epithelial neoplasia research. Convergence: COX / inflammatory signalling, Angiogenesis.

Research Context

  1. Hallmarks. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. https://doi.org/10.1016/j.cell.2011.02.013
  2. NEPC. Beltran H, et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 2016;22(3):298-305. https://doi.org/10.1038/nm.4045
  3. Metformin oncology. Pollak MN. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012;2(9):778-790. https://doi.org/10.1158/2159-8290.CD-12-0263

This oncology atlas is educational. Pathway maps, adjunctive strategies, and compound listings describe mechanistic relevance. They do not establish clinical efficacy, do not recommend treatment, and are not a substitute for oncology care. Evidence tiers are not equivalent.