pathways

KEGG's AML map shows the two hits that turn a normal blood stem cell into a leukaemia: a growth signal jammed on (FLT3, KIT or RAS) plus a broken maturation switch (fusion proteins such as PML-RARA or AML1-ETO, or mutated CEBPA and RUNX1). Drugs now exist for both halves.

Androgen receptor signalling is prostate cancer's engine. Testosterone becomes DHT, binds the androgen receptor, and drives growth genes. Castration removes the fuel; newer pills block the receptor or the enzyme that makes fuel inside the tumour.

How the immune system sees cancer, and how cancer learns to hide. Tumours display fragments of their proteins on MHC molecules; T cells kill the ones they recognise; the survivors are the ones that stopped showing fragments or switched on brakes.

Autophagy is the cell's recycling programme. Cancer cells, especially pancreatic and RAS-driven tumours, use it to survive starvation and drug stress, which is why hydroxychloroquine, an old malaria drug that blocks it, keeps appearing in trials.

The B-cell receptor is the survival switch of B cells. Signals from it pass through BTK to free NF-kappa-B, which keeps the cell alive. B-cell cancers hold it on; BTK inhibitors, proteasome inhibitors and lenalidomide each cut the line at a different point.

KEGG's basal cell carcinoma map is the Hedgehog pathway: loss of the brake PTCH1 or activation of SMO leaves GLI transcription factors permanently on. Hedgehog inhibitors (vismodegib, sonidegib) shut this down in advanced disease.

Tens of thousands of times a day a single DNA letter is oxidised or chemically scarred. A small crew snips it out and PARP marks the nick so it gets sealed. PARP inhibitors do not just switch PARP off; they trap it on the DNA, turning a harmless nick into a lethal break when the cell copies its DNA.

Every organ keeps its lining cells behind a thin, dense sheet of protein called the basement membrane. A tumour that has not crossed it is 'in situ' and essentially curable; crossing it is the moment cancer becomes invasive.

Chronic myeloid leukaemia is caused by one broken gene: two chromosomes swap pieces and glue a kinase (ABL1) to a protein that forces it permanently on. Imatinib, the first drug to target it, turned a fatal disease into a manageable one, and later drugs cover the mutations that escape it.

KEGG's bladder cancer map shows two routes: low-grade papillary tumours driven by FGFR3 or HRAS activating the MAPK relay, and high-grade invasive tumours that lose TP53 and RB1. Erdafitinib targets the first route; antibody-drug conjugates and PD-1 antibodies now anchor treatment of the second.

KEGG's breast cancer map lays out the three clinical subtypes as signalling routes: oestrogen receptor driving cyclin D and CDK4/6 in hormone-receptor-positive disease, HER2 driving PI3K/AKT and MAPK in HER2-positive disease, and EGFR, Notch, Wnt and BRCA defects in triple-negative disease. Each route has its own drug class.

The wasting syndrome that kills up to a third of cancer patients: tumours send hormonal signals (GDF-15, IL-6) that switch off appetite and burn muscle and fat. The first drug to reverse it, ponsegromab, showed weight gain in 2024.

Cancer cells rewire how they eat. They burn glucose inefficiently but fast (the Warburg effect), gorge on glutamine and fats, and build the nucleotides and lipids needed to divide. This is why the FDG PET scan works, and why metabolism is a drug target.

Cancer neuroscience is the study of how tumours talk to nerves. Nerves grow into tumours and feed them signals; brain tumours even wire themselves into neural circuits. Cutting the conversation with common drugs such as beta-blockers is now being tested.

Some cancer cells behave like stem cells: they can regrow the whole tumour, resist treatment, and switch identities. This plasticity explains why tumours come back and why some lung and prostate cancers transform into a different cancer type under therapy.

Macrophages eat cells that look wrong unless the cell shows CD47, a 'don't eat me' badge that binds SIRP-alpha. Leukaemias, myelodysplastic syndromes, lymphomas and carcinomas overproduce CD47 to escape being eaten; antibodies that cover the badge work in the lab, but the leading drug, magrolimab, failed in blood cancers because red cells wear the same badge and lose it too.

Damaged cells can stop dividing permanently instead of dying. That protects against cancer at first, but senescent cells linger, secrete inflammatory signals, and after chemotherapy can help tumours relapse, so removing them (senolytics) is a new strategy.

cGAS-STING is the cell's alarm for DNA in the wrong place. Radiation, chemotherapy, and ADCs spill DNA into the cytoplasm; cGAS detects it, STING sounds the alarm, and interferon calls in the immune system.

This KEGG map shows how chemicals in tobacco smoke, industrial pollutants, plastics and hormones cause cancer without directly damaging DNA: they switch on receptors that drive growth signalling. It matters because these routes explain part of the cancer burden from smoking, dioxins and hormone exposure, and several of the receptors are druggable.

This KEGG map shows how cancer cells rewire the handling of choline, a nutrient used to build cell membranes, so that growth signals and membrane building feed each other. It matters because the resulting build-up of phosphocholine is visible on MR spectroscopy and PET scans and is one of the metabolic hallmarks of cancer.

Most cancers have the wrong number of chromosomes and keep shuffling them at every division. This chaos fuels evolution and drug resistance, but it also stresses the cell and can trigger immune alarms, a double edge that researchers are trying to exploit.

KEGG's CML map is built around one fusion protein, BCR-ABL1, a kinase that never switches off and drives RAS, PI3K and STAT5 signalling. Because a single enzyme causes the disease, a single class of pill (imatinib and its successors) controls it in most patients.

Cells run on a 24-hour clock that gates cell division, DNA repair, and drug metabolism. Cancers often break their clocks, and the time of day a drug or immunotherapy is given can change how well it works.

A tumour is a population that evolves by natural selection. Treatment kills the sensitive cells and selects the rest, which is why resistance is the rule; measuring the surviving population (MRD) and adapting therapy is the counter-strategy.

As we age, blood stem cells with cancer-like mutations quietly expand in most people. These clones raise leukaemia and heart disease risk, are accelerated by chemotherapy, and confuse blood tests for cancer DNA.

Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.

This KEGG map traces the step-by-step genetic route from normal bowel lining to colorectal cancer: APC loss unleashes Wnt, KRAS mutation drives growth, then TP53 and TGF-beta/SMAD4 loss remove the last brakes, or alternatively mismatch repair fails and mutations pile up. Knowing which route a tumour took decides which drugs work.

Complement is a cascade of blood proteins that punches holes in things marked by antibodies and calls in inflammatory cells. Therapeutic antibodies such as rituximab use it to kill cancer cells; tumours defend themselves with shields (CD46, CD55, CD59), and the cascade's own by-products (C5a) can recruit the myeloid cells that protect the tumour.

The DNA damage response is the cell's set of repair crews. Single-strand breaks are patched by PARP; double-strand breaks by BRCA-dependent homologous recombination. Lose one crew and the cell survives; lose both and it dies. That is how PARP inhibitors work.

Before a cell divides it must copy three billion letters of DNA exactly once, 'licensing' thousands of start points in advance and firing them in waves. Cancers driven by MYC, cyclin E or RAS fire excess start points too fast, and antimetabolites such as 5-FU, topoisomerase poisons such as irinotecan and platinum drugs all jam this copying machinery.

Cancers copy their DNA too fast and with broken checkpoints, so replication forks stall and collapse. They survive only by leaning on emergency repair kinases such as ATR, CHK1, and WEE1, which is why blocking those kinases can be selectively lethal.

A break through both strands of DNA is the most dangerous lesion a cell faces. Two crews compete to fix it: homologous recombination copies the answer from the sister chromosome (accurate, needs BRCA), while end joining simply glues the ends (fast, sloppy). Which crew wins decides whether PARP inhibitors and radiation kill the cell.

Of the thousands of mutations in a tumour, only a handful (typically 2-8) actually drive it. Drivers either jam an accelerator on (oncogenes, one hit is enough) or remove a brake (tumour suppressors, both copies must go). Everything else is a passenger along for the ride.

Cancer cells can install pumps in their outer membrane that throw chemotherapy back out as fast as it comes in. The same pumps guard the gut, brain and bone marrow in healthy tissue, which is why blocking them failed as a strategy and why drug designers now choose payloads the pumps cannot grip.

Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation: they go quiet, stop dividing, and wait. These persisters are the seed of relapse. They are hard to kill precisely because they are not doing much, but they have their own weaknesses.

KEGG's endometrial cancer map shows oestrogen-related type I tumours with PTEN loss, KRAS and beta-catenin mutations and faulty mismatch repair, and type II tumours with TP53 mutation and HER2 amplification. Immunotherapy for mismatch-repair-deficient tumours and HER2-directed therapy follow directly from this split.

Cancer changes not just its genes but how they are read: chemical tags on DNA and histones silence guardians and awaken growth programmes. Unlike mutations, these changes are reversible, which is the hope behind epigenetic drugs.

How a cancer cell changes shape to migrate and to shrug off drugs. Transcription factors like ZEB1 and SNAIL loosen the cell, switch on pumps that eject chemotherapy, and hide it from the immune system.

Immune cells kill by touch: they present FAS ligand or TRAIL to a target cell, whose death receptors then trigger self-destruction from the outside in. Tumours cut this wire by deleting the receptors or over-producing decoys and blockers.

Cells can die in several programmed ways. Beyond the classic apoptosis, ferroptosis kills through iron-driven fat oxidation, and drug-resistant, mesenchymal cancer cells turn out to be unusually prone to it.

Fibroblast growth factor receptors are growth antennas on the cell surface. Bladder cancer mutates FGFR3, bile duct cancer fuses FGFR2 to other genes, and stomach cancer overproduces FGFR2b; each has its own drug, and each brings a tell-tale side effect (high phosphate) because the same receptors control phosphate in the kidney.

Tumours recruit the body's repair cells, fibroblasts, and keep them in wound-healing mode forever. The scar tissue they lay down (desmoplasia) squeezes blood vessels shut, walls out immune cells, stiffens the tissue in a way that itself tells cancer cells to grow, and is why pancreatic cancer is so hard to treat.

Cancer often arises from a whole region of tissue that already carries mutations, not from one rogue cell. Sun-exposed skin, smokers' airways, and Barrett's oesophagus are patchworks of mutant clones competing long before a tumour appears.

This KEGG map splits stomach cancer into two routes: the intestinal type that accumulates TP53, APC and HER2 changes step by step, and the diffuse type driven by loss of the cell glue E-cadherin plus MET or FGFR2 amplification. It matters because HER2, FGFR2, claudin 18.2 and PD-1 status now decide first-line treatment.

This KEGG map shows the two genetic roads to glioblastoma: primary tumours amplify EGFR and lose PTEN and p16, secondary tumours from lower-grade astrocytomas over-express PDGF and CDK4 and lose TP53 and RB. It explains why growth-factor and cell-cycle drugs are the main targeted options in brain tumours, and why paediatric low-grade gliomas with BRAF changes respond to MAPK inhibitors.

After glucose, glutamine is the tumour's favourite food. It feeds the energy cycle, donates nitrogen for making DNA letters, and makes the antioxidant glutathione. MYC- and KRAS-driven cancers eat so much of it that they starve the T cells next door.

A developmental pathway that shapes embryos and is switched back on in basal cell skin cancer and some brain tumours. Blocking it cures most advanced basal cell carcinomas, but tumours learn to reactivate it downstream.

This KEGG map shows how hepatitis viruses, alcohol and aflatoxin leave the liver with mutations in telomerase, TP53, Wnt/beta-catenin, PI3K/AKT/mTOR and the oxidative stress sensor NRF2, which together drive liver cancer. It matters because the map explains why liver cancer is treated mainly with angiogenesis blockers and immunotherapy rather than a single targeted drug.

The pathway that tells organs when to stop growing. Cancers disable it so YAP and TAZ stay in the nucleus driving growth; in mesothelioma, NF2 loss does exactly that, and the first drugs against the YAP-TEAD switch are in trials.

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.

Getting into the bloodstream kills almost every cell that tries: cells are ripped from their neighbours, battered by flow, and hunted by NK cells. Fewer than one in a thousand survive. The ones that do travel in clusters, wear a cloak of platelets, or ride with neutrophils. Liquid biopsies catch what is left.

Intrinsic apoptosis is the cell's self-destruct switch. BCL-2 holds it shut; BAX and BAK pull it open. Venetoclax pries BCL-2 off so the switch can fire.

To invade, a cancer cell must grip the scaffolding around it, dissolve a path with enzymes, and pull itself forward, alone or in a chain led by a scout cell. Fibroblasts often cut the trail first. The enzyme blockers of the 1990s failed; today's targets are the grip (integrins, FAK) and the trail-makers.

The relay that turns cytokine signals into gene changes. Overactive in blood cancers (JAK2 in myelofibrosis), it is also the wire that carries interferon's cancer-killing message, so tumours cut it to escape immunotherapy.

KEAP1-NRF2 is the cell's antioxidant defence switch. Lung cancers often break the off-switch (KEAP1), leaving NRF2 permanently on, which detoxifies chemotherapy and radiation and makes these tumours resistant to almost everything.

Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.

Dividing cells need membranes, and membranes are fat. Cancers switch on the fat-building enzymes most adult tissues keep off, and in fatty environments (breast, omentum, bone marrow) they also steal lipids from neighbouring fat cells. This links obesity to cancer and offers new drug targets.

KEGG's melanoma map shows BRAF or NRAS mutations driving the MAPK growth relay, PTEN loss driving PI3K/AKT, and loss of the CDKN2A brakes (p16 and p14ARF) on CDK4/6 and p53. BRAF plus MEK inhibitors and immune checkpoint antibodies have transformed treatment.

In some leukaemias a broken chromatin protein (KMT2A, once called MLL) or a mutant NPM1 keeps embryonic growth genes (HOXA9, MEIS1) switched on, so blood cells never mature. Both need a partner called menin to stay on the DNA. Menin inhibitors pull the plug and the cells mature; the first was approved in 2024.

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.

This KEGG map collects the small RNA molecules (microRNAs) that are switched up or down in nine common cancers and shows which oncogenes and tumour suppressors they silence. It matters because a single microRNA can dial down dozens of genes at once, so losing or gaining one reshapes whole signalling routes.

After DNA is copied, a proofreading crew fixes the letters the polymerase got wrong. Lose it and the genome fills with thousands of small errors, especially in repetitive stretches (microsatellites). Those errors make abnormal proteins that the immune system can see, which is why immunotherapy works so well in these cancers.

When a cell divides, a scaffold of microtubules (the spindle) pulls one copy of each chromosome to each side. A checkpoint holds the split until every chromosome is hooked on. Taxanes and vinca alkaloids freeze the spindle so the cell is stuck at this checkpoint until it dies.

Cancer cells must make protein at furious speed. The eIF4F complex that starts protein synthesis is the funnel where growth signals converge, and drugs that pinch the funnel starve the tumour of the proteins it needs most.

Every cause of DNA damage leaves its own fingerprint in the genome: sunlight, tobacco, a faulty repair enzyme, a gut bacterium. Reading these fingerprints tells you what caused a cancer and which repair crews it is missing, which in turn predicts which drugs will work.

A single mutation in a metabolic enzyme (IDH1 or IDH2) makes cells pour out a molecule they should never make, 2-hydroxyglutarate. It jams the machinery that erases chemical marks on DNA and histones, so blood and brain cells get stuck before they mature. Pills that block the mutant enzyme let them mature again.

MYC is the most commonly amplified cancer gene, a master switch that turns on thousands of growth genes. It has no pocket for a conventional drug, so it remained 'undruggable' for 40 years; the first direct MYC drugs finally entered trials in the 2020s.

Tumours recruit the body's clean-up cells (macrophages and immature myeloid cells) and re-train them as bodyguards. They switch off T cells, build vessels, and, when a therapeutic antibody flags a cancer cell for eating, are told 'don't eat me' by CD47 on its surface.

Natural killer cells patrol for cells that have lost their identity papers (MHC-I) or that display stress flags. Cancers that hide from T cells by dropping MHC-I become visible to NK cells, unless they also shed the stress flags, wrap themselves in a second inhibitory badge (HLA-E), or soak the neighbourhood in TGF-β.

KEGG's non-small cell lung cancer map shows a set of alternative on-switches (EGFR mutation, KRAS mutation, EML4-ALK, RET and MET alterations) that all feed the same RAS/ERK, PI3K/AKT and STAT relays, plus loss of the p16 and p53 brakes. Each on-switch now has its own targeted pill, which is why molecular testing comes before treatment.

A cell-to-cell contact signal that decides cell fate. It drives T-cell leukaemia when mutated on, acts as a tumour suppressor in some squamous cancers when lost, and its ligand DLL3 became a drug target in small-cell lung cancer.

Tumours and immune cells eat from the same plate. Cancer cells hoard glucose and glutamine, dump lactate and acid, and burn tryptophan and arginine into by-products that paralyse T cells. The tumour wins the food fight, and the immune system loses before it has fired a shot.

In hormone-positive breast cancer, oestrogen binds its receptor, which switches on genes that make the cell divide. Every endocrine therapy cuts this chain somewhere.

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.

Breast cancer goes to bone, lung, liver and brain; prostate cancer to bone; colon cancer to liver; uveal melanoma almost only to liver. Paget's 1889 idea still holds: where a cancer spreads depends on both the seed (the cell's programme) and the soil (the organ's welcome). Each soil has its own vicious cycle, and some are druggable.

The p53 and RB checkpoints are the cell's brakes. p53 senses damage and stops the cell from copying itself; RB holds the cell at the G1 gate until CDK4/6 unlocks it. Cancers cut these brakes.

This KEGG map shows the order of genetic hits that turn normal pancreatic duct cells into ductal adenocarcinoma: KRAS mutation first, then loss of the p16 brake, then loss of TP53, SMAD4 and BRCA2. It matters because nearly every pancreatic cancer is driven by KRAS, which until recently had no drug.

How T cells decide to attack. A T cell needs to see the target (TCR-MHC) and get a 'go' signal (CD28). PD-1 and CTLA-4 are 'stop' signals; tumours exploit them. Checkpoint inhibitors remove the stop.

The cell's 'grow and survive' circuit. Growth signals from the surface switch on PI3K, which switches on AKT, which switches on mTOR, which builds proteins and blocks self-destruction.

KEGG's prostate cancer map centres on the androgen receptor, the hormone switch that prostate cells depend on, plus loss of PTEN and NKX3.1 that lets PI3K/AKT growth signalling run free. Hormone therapy, AR antagonists and now AKT inhibitors act on these two arms.

This KEGG map shows how sugar-coated proteins on the cell surface and in the surrounding matrix (proteoglycans such as syndecans, glypicans, CD44 and decorin) catch growth factors and hand signals to receptors. It matters because these molecules set how loudly growth signals reach the tumour cell and how easily it invades.

The RAS-MAPK pathway is the cell's 'divide' relay. A signal at the surface flips RAS on, which passes to RAF, MEK, and ERK, which tell the nucleus to make the cell divide. KRAS and BRAF mutations jam it in the on position.

Growth-factor receptors are antennas on the cell surface that pair up when a signal lands and switch on the growth relays inside. Cancers mutate, multiply, or fuse these antennas so they broadcast 'grow' with no signal at all. Most targeted drugs, antibodies and ADCs start here.

KEGG's kidney cancer map shows how losing VHL lets the oxygen sensor HIF pile up and order new blood vessels (VEGF, PDGF), while MET and PI3K drive growth in other subtypes. Anti-VEGF drugs, HIF-2a inhibitors and immunotherapy all act on this circuit.

When a drug blocks a cancer's engine, the cancer has five ways back: change the part the drug binds, make more of it, take a side road, switch to a different engine altogether, or stop letting the drug in. Knowing which route a tumour took decides the next drug.

Genes are cut and pasted into messages before they are used. Blood cancers often carry mutations in the splicing machinery, and the errors create abnormal proteins that could serve as targets or immune flags.

KEGG's small cell lung cancer map shows a tumour with both master brakes removed, RB1 and TP53, plus amplified MYC pushing the cell cycle and PTEN loss and BCL2 keeping cells alive. Chemotherapy with PD-L1 antibodies and the DLL3 T-cell engager tarlatamab are the current answers.

A machine that opens and closes DNA so genes can be read. One in five cancers has a broken part (ARID1A, SMARCA4, PBRM1), and losing one part often creates a dependence on its twin, which is the basis for new synthetic-lethal drugs.

Two genes are synthetically lethal when losing either alone is fine but losing both kills the cell. Cancers that have already lost one (a tumour suppressor you cannot put back) become uniquely dependent on the other, which you can drug. BRCA and PARP was the first proof; a dozen more pairs are now in trials.

T cells that see their target for weeks on end without winning gradually shut down: they raise a set of brakes (PD-1, LAG-3, TIM-3, TIGIT), lose their ability to kill, and eventually lock this state into their DNA. Checkpoint drugs rescue the ones that are only partly exhausted; the terminally exhausted are beyond reach.

Normal cells can divide only a limited number of times because the protective caps on their chromosomes, telomeres, wear down. About 90% of cancers switch the cap-rebuilding enzyme telomerase back on, often through TERT promoter mutations, and roughly 10% use an alternative lengthening route (ALT), so they divide indefinitely; imetelstat is the first approved telomerase inhibitor.

A signal that stops normal cells from dividing but, once a cancer is established, switches sides: it builds scar-like stroma, walls out immune cells, and pushes cells into a migratory state.

A tumour cannot grow beyond a couple of millimetres without its own blood supply. The 'switch' flips when the signals calling for new vessels (VEGF, FGF, angiopoietin) outweigh the ones holding them back (thrombospondin). The vessels that result are leaky and chaotic, which starves the tumour of oxygen, blocks drugs, and gives cancer cells a way out.

The brain's blood vessels are sealed tight and fitted with pumps that eject most drugs. That protects the brain from poisons but also from chemotherapy and antibodies. Cancer cells that do squeeze through recruit the brain's own support cells, astrocytes, to feed and shield them.

Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.

Cell division runs on a clock made of cyclins and their kinases (CDKs), each pair firing in order: D-CDK4/6 to leave rest, E-CDK2 to start copying DNA, A-CDK2 to finish, B-CDK1 to divide. Cancers speed the clock; CDK inhibitors slow it.

To make a good antibody, a B cell has to deliberately damage its own DNA and keep dividing while it does. The germinal centre is where that happens, under strict time limits. Most B-cell lymphomas are cells that went through it and did not come out.

How cancer spreads: cells leave the tumour, squeeze into blood or lymph vessels, survive the journey, exit into a new organ, often sleep there for years, and finally grow. Metastasis causes about 90% of cancer deaths.

p53 is the cell's emergency coordinator: DNA damage, oncogene stress or lack of oxygen switch it on, and it then pauses division, orders repairs, or triggers suicide or permanent retirement, while MDM2 keeps it off in healthy cells. About half of cancers mutate p53 outright, and sarcomas, gliomas, melanomas and retinoblastomas silence it instead by amplifying MDM2 or MDM4.

Before a single cancer cell arrives, the primary tumour sends parcels ahead: tiny vesicles (exosomes) and hormones that recruit bone-marrow cells to a distant organ and remodel it into fertile soil. By the time the seed lands, the bed is already made.