{"slug":"theory","tag":"theory","variants":["theory"],"description":"No description yet","count":17,"kinds":{"pathway":1,"term":16},"related":[{"slug":"mechanics-atlas","tag":"mechanics-atlas","shared":1},{"slug":"mechanism","tag":"mechanism","shared":1}],"records":[{"id":"theories-of-cancer","kind":"pathway","name":"Theories of cancer: how the ideas connect","route":"/pathways/theories-of-cancer/","tldr":"Scientists have given more than a dozen answers to what cancer is: mutated genes, runaway evolution, misbehaving stem cells, disordered tissue, ancient cell programmes, broken chromosomes, metabolism, epigenetic switches, unhealed wounds, a failed immune system, ageing tissue, force or electricity. This map shows each theory, who proposed it, what held up, and how the ideas connect."},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","route":"/terms/somatic-mutation-theory/","tldr":"The standard account: cancer begins when a single body cell picks up mutations in the genes that control growth, and its descendants inherit them. It explains why carcinogens are mutagens, why cancer risk runs in some families and why drugs aimed at a mutated gene can work, but it cannot by itself explain why normal tissue full of the same mutations does not become cancer."},{"id":"driver-passenger-model","kind":"term","name":"Driver and passenger mutations: the refined somatic mutation theory","route":"/terms/driver-passenger-model/","tldr":"When whole cancer genomes were read, tumours turned out to carry thousands of mutations, of which only a handful drive growth; the rest are passengers that happened to be in the cell. The refinement made the somatic mutation theory precise and testable, and it is the basis of genomic profiling and of matching drugs to mutations."},{"id":"clonal-evolution-theory","kind":"term","name":"Clonal evolution and the ecological view of cancer","route":"/terms/clonal-evolution-theory/","tldr":"A tumour is a population of cells that mutate, compete and are selected, exactly as species are, and treatment is one more selective pressure. Peter Nowell proposed this in 1976; it explains why tumours are mixtures of clones, why resistance to almost any single drug appears, and why some researchers now try to steer a tumour's evolution rather than eradicate it."},{"id":"hallmarks-synthesis","kind":"term","name":"Hallmarks of cancer as a synthesis of the theories","route":"/terms/hallmarks-synthesis/","tldr":"Rather than asking what starts cancer, Hanahan and Weinberg asked what every cancer ends up able to do: keep growing, ignore stop signals, avoid death, live forever, grow vessels, invade, rewire metabolism and hide from the immune system. Each update has absorbed a rival theory into the list, so the hallmarks read as the field's working synthesis rather than a theory of cause."},{"id":"cancer-stem-cell-theory","kind":"term","name":"Cancer stem cell theory and phenotypic plasticity","route":"/terms/cancer-stem-cell-theory/","tldr":"The idea that a tumour is organised like a tissue, with a small pool of stem-like cells that renew it and a bulk that cannot, so killing the bulk shrinks the tumour but the stem-like cells regrow it. Proved in leukaemia and real in some solid tumours, but the rigid hierarchy gave way to plasticity: ordinary tumour cells can slip back into the stem-like state, especially under treatment."},{"id":"epigenetic-progenitor-theory","kind":"term","name":"Epigenetic progenitor theory: cancer without a first mutation","route":"/terms/epigenetic-progenitor-theory/","tldr":"The proposal that cancer begins not with a mutation but with a reversible change in how genes are switched on and off in a stem or progenitor cell, which then makes later mutations more likely and more dangerous. It explains cancers with almost no mutations and why cells can switch state under treatment, and it produced the epigenetic drugs used in blood cancers."},{"id":"aneuploidy-theory-of-cancer","kind":"term","name":"Aneuploidy and chromosomal instability as the cause of cancer","route":"/terms/aneuploidy-theory-of-cancer/","tldr":"The oldest theory of cancer, from Theodor Boveri in 1914: tumours arise from cells with the wrong number or arrangement of chromosomes. Peter Duesberg revived it in the 1990s as an alternative to gene mutations. Most solid tumours are indeed aneuploid and chromosome shattering can create several drivers at once, but chromosomal chaos is now read as an accelerator of evolution, not the sole cause."},{"id":"metabolic-theory-of-cancer","kind":"term","name":"Metabolic theory of cancer: from Warburg to oncometabolites","route":"/terms/metabolic-theory-of-cancer/","tldr":"Otto Warburg noticed a century ago that cancer cells ferment glucose even when oxygen is plentiful and concluded that damaged respiration causes cancer. The observation held and became the basis of PET scanning, but the causal claim did not: most cancers rewire metabolism because mutated signalling demands building blocks, and only a few metabolic enzymes are themselves cancer genes."},{"id":"tissue-organisation-field-theory","kind":"term","name":"Tissue organisation field theory (Sonnenschein and Soto)","route":"/terms/tissue-organisation-field-theory/","tldr":"Carlos Sonnenschein and Ana Soto argue that cancer is a disease of tissue architecture, not of single cells: carcinogens disrupt the conversation between a tissue's supporting stroma and its lining cells, and disordered growth follows as in a wound or an embryo gone wrong. Mutations are consequences. Their rat experiments are real, but the theory has few followers and no drug of its own."},{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","route":"/terms/microenvironment-inflammation-theory/","tldr":"A tumour is not a lump of cancer cells but a tissue: fibroblasts, vessels and immune cells, recruited by the signals a wound uses and never told to stop. Virchow saw white cells in tumours in 1863; Dvorak called tumours 'wounds that do not heal' in 1986. It explains why chronic inflammation causes about a fifth of cancers and why aspirin, HPV and hepatitis vaccines and anti-angiogenic drugs work."},{"id":"seed-and-soil-hypothesis","kind":"term","name":"Seed and soil hypothesis of metastasis (Paget)","route":"/terms/seed-and-soil-hypothesis/","tldr":"Stephen Paget asked in 1889 why breast cancer spread to some organs more than blood flow could explain, and answered that a travelling cancer cell (the seed) grows only where the organ (the soil) suits it. Ignored for most of a century, then confirmed: each cancer has favoured destinations, tumours prepare distant organs before cells arrive, and drugs that change the soil reduce bone metastases."},{"id":"immune-surveillance-immunoediting","kind":"term","name":"Immune surveillance and cancer immunoediting","route":"/terms/immune-surveillance-immunoediting/","tldr":"The immune system patrols for cells that have turned malignant and destroys most of them; the tumours we see are the ones that learned to hide. Ehrlich guessed this in 1909, Burnet and Thomas argued it in the 1950s, it was declared dead in the 1970s, and Robert Schreiber's mouse experiments revived it in 2001. Checkpoint inhibitors, which can cure some metastatic melanoma, are its vindication."},{"id":"ageing-tissue-field-theory","kind":"term","name":"Ageing tissue and clonal fields: cancer as a disease of old tissue","route":"/terms/ageing-tissue-field-theory/","tldr":"Sequencing of healthy skin, gullet and blood shows that by middle age they are patchworks of mutant clones, many carrying classic cancer mutations, yet cancer stays rare until old age. The ageing tissue view says the mutations are there early and it is the tissue that changes: ageing, damage and inflammation alter which clones win. Clonal haematopoiesis in the blood is the best-measured example."},{"id":"atavistic-theory-of-cancer","kind":"term","name":"Atavistic theory: cancer as a reversion to an ancient programme","route":"/terms/atavistic-theory-of-cancer/","tldr":"Physicist Paul Davies and astrobiologist Charles Lineweaver proposed in 2011 that cancer is not a new invention by each tumour but the re-awakening of an ancient survival toolkit from the earliest multicellular life, about a billion years old, which is why every cancer behaves in the same few ways. Gene-age studies give it some support; whether it predicts anything a doctor can use is unproven."},{"id":"mechanical-theory-of-cancer","kind":"term","name":"Mechanical theory: stiffness, pressure and force as causes","route":"/terms/mechanical-theory-of-cancer/","tldr":"Cancer cells feel their surroundings. A stiff, dense matrix or a compressed tissue is not just a symptom but a signal that pushes cells towards malignancy, and pressure inside tumours squeezes vessels shut so drugs and oxygen cannot get in. Bissell and Weaver reverted cancer cells to normal by blocking the matrix; Rakesh Jain made solid stress and vessel normalisation a treatment strategy."},{"id":"bioelectric-theory-of-cancer","kind":"term","name":"Bioelectric theory of cancer (Levin)","route":"/terms/bioelectric-theory-of-cancer/","tldr":"Cells hold a voltage across their membranes, and tissues share these voltages as patterns that guide growth and regeneration. Michael Levin proposes that cancer is a breakdown of this pattern: tumour cells are depolarised, and in tadpoles restoring the voltage with light-controlled ion channels prevented and reversed tumours caused by mutant KRAS. Striking animal results; no human evidence yet."}]}