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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.
The claim. Two premises. First, proliferation is the default state of all cells, as it is in single-celled organisms, and multicellular tissues actively restrain it; cancer is a failure of restraint, not the gain of a growth signal. Second, carcinogenesis happens at the tissue level of organisation: carcinogens damage the reciprocal signalling between stroma and parenchyma (the 'morphogenetic field'), and the resulting disorganisation allows cells to revert to their default of proliferation and motility. Genomic changes are downstream. Because the disease is architectural, it should be reversible by restoring normal tissue interactions.
Who and when. Sonnenschein and Soto, The Society of Cells, 1999; Theories of carcinogenesis: an emerging perspective, 2008; Soto and Sonnenschein, The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory, 2011. The theory draws on earlier work by Mina Bissell on the microenvironment and on Smithers' 1962 argument that cancer is a disease of organisation.
Evidence for. Maffini, Soto and Sonnenschein showed in 2004 that in rats, exposing the mammary stroma to a carcinogen and then transplanting unexposed epithelium produced tumours, while exposing the epithelium and transplanting it into unexposed stroma did not. Mintz and Illmensee (1975) made normal mice from malignant teratocarcinoma cells injected into blastocysts. Weaver and Bissell (1997) reverted malignant breast cells to normal architecture in three-dimensional culture by blocking beta-1 integrin. Normal tissue tolerates driver mutations without cancer (Martincorena), and Bissell and Hines asked in 2011 why, given how many mutations we carry, we do not get more cancer.
Evidence against and limits. Single genetic lesions are sufficient to cause cancer in many settings: BCR::ABL1 transgenic mice develop leukaemia, hereditary retinoblastoma follows two hits in RB1, and viral E6 and E7 transform cells by disabling p53 and RB. Almost all human tumours are clonal and carry drivers, which is easier to explain if the mutated cell is the unit of selection. The premise that proliferation is the default of animal cells is disputed. The strong form is hard to falsify and has produced no specific therapy. Most cancer biologists regard the tissue-level findings as part of the microenvironment view rather than a replacement for the mutation theory.
Predictions that held or failed. Held: the stroma is a target of carcinogens and a determinant of whether mutant cells become tumours; fibroblasts and matrix drive progression. Failed or unfulfilled: reversion of established human carcinomas by correcting tissue context has not been achieved clinically; the prediction that mutations would prove incidental has not survived sequencing.
Therapies that came from it. None directly. Its programme is pursued through stromal and matrix-directed treatments (fibroblast and desmoplasia targeting, stromal decompression in pancreatic cancer), through differentiation therapy and through the mechanical theory, and its central experiments are cited by the microenvironment and inflammation view.
Status: contested. A minority position whose experiments are respected and whose critique of cell-centred thinking has been absorbed into the microenvironment and hallmarks frameworks, but whose claim to replace the somatic mutation theory is not accepted.
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One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
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Shares Hallmarks of cancer as a synthesis of the theories, Microenvironment and inflammation: tumours as wounds that do not heal, Theories of cancer: how the ideas connect and the tag theory.
Shares Hallmarks of cancer as a synthesis of the theories, Theories of cancer: how the ideas connect, Somatic mutation theory of cancer and the tag theory.
Shares Microenvironment and inflammation: tumours as wounds that do not heal, Theories of cancer: how the ideas connect and the tag theory.