Hallmarks of Cancer
TL;DR
The Hallmarks of Cancer framework (Hanahan & Weinberg, 2000; Hanahan 2011; Hanahan 2022) organizes cancer’s acquired capabilities into 14 discrete hallmarks. This hub note is the entry point for all cancer biology in the Vitals vault. No peptide in this program has Phase I human evidence for anticancer efficacy. The framework is descriptive — mapping a peptide to a hallmark does not make it a cancer treatment.
Why It Matters for Vitals
Cancer biology is relevant to Vitals in two primary ways:
- Safety gating — Peptide recommendations must be blocked or flagged for clinical consultation when users have active cancer, dysplasia, or cancer history (NED). This hub anchors the safety tier framework.
- Mechanistic mapping — The hallmarks framework lets us reason about where each peptide touches cancer biology, even when the connection is theoretical.
The hallmarks do not generate recovery scores, readiness modifiers, or strain algorithm inputs. Their value is framing and safety.
The 14 Hallmarks (2022)
| # | Hallmark | Core Mechanism |
|---|---|---|
| H1 | Sustaining Proliferative Signaling | Oncogenes (RAS, EGFR, PI3K/AKT/mTOR) maintain chronic proliferation |
| H2 | Evading Growth Suppressors | Loss of p53, RB, PTEN; resistance to TGF-β |
| H3 | Resisting Cell Death | BCL-2 family overexpression; caspase evasion; apoptosis blockade |
| H4 | Enabling Replicative Immortality | Telomerase reactivation or ALT mechanism |
| H5 | Inducing Angiogenesis | VEGF, FGF, PDGF secretion; tumor vascularization |
| H6 | Activating Invasion & Metastasis | EMT (SNAIL, SLUG, ZEB1/2); MMPs; cadherin switching |
| H7 | Genome Instability & Mutation | BRCA1/2, MMR, APOBEC — mutational burden accumulation |
| H8 | Tumor-Promoting Inflammation | TAMs (M2), MDSCs, NF-κB activation; COX-2/PGE2 |
| H9 | Unlocking Phenotypic Plasticity | Dedifferentiation; disrupted differentiation programs |
| H10 | Senescent Cells (SASP) | Senescence-associated secretory phenotype — creates pro-tumor niche |
| H11 | Noncoding Mutations | Telomere promoter mutations; regulatory region alterations |
| H12 | Altered ECM & Mechanotransduction | ECM remodeling; CAFs; integrin signaling; mechanotransduction |
| H13 | Polymorphic Microbiomes | Gut barrier dysfunction; LPS; short-chain fatty acids |
| H14 | SASP in Metastasis | SASP from senescent cells at distant sites creates metastatic niche |
Canonical citation: PMID 35022204 — “Hallmarks of Cancer: New Dimensions,” Cancer Discovery, January 2022.
Critical Limitation
The Hallmarks framework is descriptive, not druggable. Most hallmarks involve complex, redundant networks. The fact that a peptide mechanism maps to a hallmark does not mean the peptide is a viable cancer therapeutic.
Peptide × Hallmark Mapping Summary
| Peptide | Key Hallmark(s) | Direction | Safety Tier |
|---|---|---|---|
| PCC1 | H10, H14 | Senolytic — removes SASP cells | Tier 2 |
| Epithalon | H4, H11 | Telomerase upregulation | Tier 2 |
| BPC-157 | H5, H8 | Pro/anti-angiogenic duality; anti-inflammatory | Tier 2 |
| GHK-Cu | H7, H8, H12 | DNA repair support; anti-inflammatory; ECM remodeling | Tier 2 |
| Retatrutide | H1 | Autophagy modulation — context-dependent | Tier 2 |
| MOTS-c | H1 | Antagonizes mTOR; metabolic reprogramming | Tier 2 |
| GHRP-2, GHRP-6, CJC-1295 | H1, H6 | GH/IGF-1 axis activation — mitogenic | Tier 3 |
See Peptide Oncology Safety Tiers for full tier definitions and user guidance.
Epidemiology Benchmarks (Efficacy Ceiling)
| Cancer Type | Stage | 5-Year Survival | Standard of Care |
|---|---|---|---|
| All cancers (distant) | IV | 22–35% | Variable |
| Breast | IV | 22–30% | Endocrine + CDK4/6i ± chemo |
| Melanoma | IV | 35% | PD-1 + CTLA-4; BRAF/MEK i |
| NSCLC | IV | 8–15% | Immunotherapy ± chemo; targeted therapy |
| Colorectal | IV | 14–18% | Chemo + bevacizumab; immunotherapy (MSI-H) |
| Pancreatic | IV | 3–5% | FOLFIRINOX; gemcitabine + nab-paclitaxel |
| All cancers (all stages) | All | 72.5% | Variable |
No peptide in this program has Phase I evidence for anticancer efficacy in humans.
Key Failure Modes
- Telomerase = immortality/cancer cure — False. Risk depends on p53 status.
- BPC-157 is anti-cancer — Unresolved angiogenesis duality.
- Autophagy upregulation cures cancer — Direction entirely context-dependent.
- Growth factors are safe for cancer survivors — IGF-1 is mitogenic; Tier 3.
- Survivorship bias in alternative oncology testimonials.
- Hallmarks ≠ druggable targets.
What This Hub Does NOT Claim
- ❌ No peptide “treats cancer”
- ❌ No peptide “cures cancer”
- ❌ No peptide has anticancer efficacy evidence in humans
- ❌ Consumer wearables cannot detect or monitor cancer
- ❌ Telomerase activation is not universally safe
Related Notes
- Peptide Oncology Safety Tiers — Safety framework for all Vitals peptides in oncology context
- Tumor Microenvironment — TME components and therapeutic barriers
- Peptides MOC — Peptide hub notes (PCC1, Epithalon, BPC-157, GHK-Cu, etc.)
- Senolytic mechanisms — Broader senolytic biology (02-Mechanisms/)
Source: Hallmarks of Cancer v2 canonical monograph (batch 20) · PMID 35022204 · SEER/ACS survival data