Viral and inflammatory causes
One cancer in eight is caused by a virus, and many more by chronic inflammation. HPV and hepatitis B carry master keys to the cell's brakes; long-running inflammation supplies growth signals and mutagens. Vaccines and anti-infectives are among the most effective anti-cancer drugs ever made.
Diagram
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
A burglar who does not need to pick the locks because he carries a master key: E6 and E7 are keys that open p53 and RB directly, saving the virus the years of mutation a spontaneous cancer needs. The upside is that the burglar's face is on every camera, so the immune system can be taught to spot him.
A wound that never heals: the repair crews keep pouring in growth signals and clearing away rubble, and a wound that is always being rebuilt is a wound where mistakes accumulate.
Soil bacteria decide whether a garden thrives. Some feed the plants' defenders, some produce poisons, and some even eat the pesticide before it reaches the weeds.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 2, How a cell becomes cancer: Cancer is evolution inside a body.
One cancer in eight is caused by a virus, and many more by chronic inflammation. HPV and hepatitis B carry master keys to the cell's brakes; long-running inflammation supplies growth signals and mutagens. Vaccines and anti-infectives are among the most effective anti-cancer drugs ever made.
Oncogenic viruses. About one cancer in eight worldwide is caused by a virus. HPV, hepatitis B and C, Epstein-Barr, HTLV-1, KSHV and Merkel cell polyomavirus each hijack the same brakes cancer normally has to mutate, which is why vaccines against HPV and HBV are among the most effective anti-cancer drugs ever made.
Inflammation & NF-κB. Chronic inflammation is soil for cancer: it feeds growth signals, DNA damage, and immune suppression. The NF-κB switch inside cells is the master relay, and colitis, hepatitis, and H. pylori gastritis are the clinical proof.
Microbiome-tumour interactions. The bacteria in the gut, and even inside tumours, influence whether cancer starts and whether immunotherapy works. Transplanting stool from responders has made some non-responders respond.
The molecular players
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.
The signalling enzyme that B-cell cancers use to survive. Blocking it turned chronic lymphocytic leukaemia into a disease controlled by a daily pill.
CDK4/6 is the engine that pushes a cell to copy its DNA. Blocking it alongside hormone therapy roughly doubled the time hormone-driven breast cancer stays controlled.
TP53 is the 'guardian of the genome', broken in half of all cancers. Fixing it directly has so far defeated every attempt, so drugs exploit what its loss makes cancers depend on.
Where medicines act
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
- CadonilimabApprovedCervical cancerGastric & gastro-oesophageal junction cancer
- CamrelizumabApprovedOesophageal cancerHepatocellular carcinomaNon-small-cell lung cancer
- Camrelizumab + rivoceranibApprovedHepatocellular carcinoma
- CemiplimabApprovedNon-small-cell lung cancerMelanomaPD-L1-high non-small-cell lung cancer without a driver mutation
- DostarlimabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaEndometrial cancerColorectal cancer
- IvonescimabApprovedNon-small-cell lung cancerColorectal cancerTriple-negative breast cancer (TNBC)
- NivolumabApprovedMelanomaNon-small-cell lung cancerRenal cell carcinoma
- PembrolizumabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaTriple-negative breast cancer (TNBC)Non-small-cell lung cancer
- +23 more at PD-1 →
- AcalabrutinibApprovedChronic lymphocytic leukaemiaDiffuse large B-cell lymphomaChronic lymphocytic leukaemia, first treatment
- IbrutinibApprovedChronic lymphocytic leukaemiaDiffuse large B-cell lymphoma
- OrelabrutinibApprovedChronic lymphocytic leukaemiaMantle cell lymphoma
- PirtobrutinibApprovedChronic lymphocytic leukaemiaDiffuse large B-cell lymphomaRelapsed or refractory chronic lymphocytic leukaemia
- ZanubrutinibApprovedChronic lymphocytic leukaemiaDiffuse large B-cell lymphomaMarginal zone lymphoma
- BexobrutidegPhase 3
- BGB-16673Phase 3
- NemtabrutinibPhase 3
- AbemaciclibApprovedHR-positive / HER2-negative breast cancerHigh-risk early HR-positive breast cancerHR-positive metastatic breast cancer after CDK4/6 inhibitors
- DalpiciclibApprovedHR-positive / HER2-negative breast cancer
- PalbociclibApprovedHR-positive / HER2-negative breast cancerHER2-positive breast cancer
- RibociclibApprovedHR-positive / HER2-negative breast cancerHigh-risk early HR-positive breast cancer
- TrilaciclibApprovedSmall-cell lung cancer
- AtirmociclibPhase 3
- LerociclibPhase 3
- TQB3616Phase 3
- +1 more at CDK4/6 →
- SelinexorApprovedEndometrial cancerMultiple myelomaDiffuse large B-cell lymphoma
- OSE2101Phase 3
- KRT-232Phase 2
- EprenetapoptNegative
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
- 2024rctNADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanomaNew England Journal of Medicinechanged practice
- 2024rctNICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2024translationalNICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2023translationalRojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longerNature
- 2023translationalTRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapseNature
- 2022rctCheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgeryNew England Journal of Medicinechanged practice
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
Open questions
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
- Why has aspirin prevented colorectal cancer in some trials and not others?
- Are there undiscovered oncogenic viruses or bacteria behind cancers of unknown cause?
- being tested at scaleresearchRandomised trials of stopping immunotherapy after one year versus continuing
Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.
- early clinicalBiomarker-directed first-line quadruplets in gastric cancer
Stomach cancer now has three add-on biomarkers (HER2, PD-L1, Claudin 18.2) that often overlap. Test whether combining two add-ons beats picking one.
- early clinicalBRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer
Add immunotherapy to the two targeted pills in the most aggressive thyroid cancer, because the combination has produced multi-year survivors in early series.
- early clinicalCD8 PET to stop or switch immunotherapy early
Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.
- early clinicalresearchConfirm ultra-low-dose immunotherapy so it can be afforded where most patients live
A single-centre trial at Tata Memorial found that adding nivolumab at about a twentieth of the usual dose to chemotherapy improved outcomes in head and neck cancer. Confirmatory trials against standard-dose immunotherapy are needed before low-dose labels could make immunotherapy affordable for millions.
- early clinicalctHPV-DNA-adapted de-escalation of chemoradiation
Instead of guessing from HPV status who can get less radiation, measure the virus DNA in blood during treatment and reduce dose only when it clears fast.
- early clinicalresearchExtended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable
Immunotherapy antibodies stay active in the body for weeks, yet are often given every two or three weeks. After a few months, spacing doses out to every two or three months might work as well, with fewer hospital visits and much lower cost.
- early clinicalGive immunotherapy in the morning
Several studies found patients infused with checkpoint inhibitors earlier in the day lived longer. If a randomised trial confirms it, it is a free improvement available everywhere tomorrow.
- early clinicalMaking microsatellite-stable colorectal cancer immunotherapy-responsive
Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.
- early clinicalMicrobiome transplant as a routine immunotherapy adjunct
Stool transplants from immunotherapy responders have rescued some non-responders in melanoma. If defined bacterial cocktails work as well, every immunotherapy patient could get one.
5 more ideas are linked to this stage's pathways, targets and terms; see the rankings →
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2025rctAMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patientsNew England Journal of Medicinechanged practice
- 2025rctCheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade laterNew England Journal of Medicinechanged practice
- 2025rctCheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanomaNew England Journal of Medicinechanged practice
- 2025rctHARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancerThe Lancet
- 2024rctEV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancerNew England Journal of Medicinechanged practice
- 2024rctKEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgeryThe Lancet
- 2024rctKEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)The Lancetchanged practice
- 2024rctKEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)The Lancetchanged practice
- 2024rctNADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanomaNew England Journal of Medicinechanged practice
- 2024rctNICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2024translationalNICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2024rctSWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adultsNew England Journal of Medicinechanged practice
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 2.6 of 56.