{"entity":{"id":"paper-reya-cancer-stem-cells-nature-2001","kind":"paper","name":"Reya 2001: stem cells, cancer and cancer stem cells","aka":[],"tldr":"The review that framed the cancer stem cell idea: only a small subset of cells in a tumour may be able to renew it, so treatments that shrink a tumour without removing those cells let it grow back.","summary":"Reya, Morrison, Clarke and Weissman set out the parallels between normal stem cells and cancer. Normal stem cells self-renew and give rise to differentiated progeny, and the same signalling pathways that control self-renewal, including Wnt, Notch and Sonic hedgehog, are recurrently altered in cancers. Drawing on experiments in which only rare, marker-defined cells from human leukaemia could re-establish the disease in mice, they proposed that many cancers are maintained by a minority of cancer stem cells and that these cells, rather than the tumour bulk, should be the target of therapy.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/35102167"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":["stem-cell","relapse-recurrence"],"trials":[],"people":["irving-weissman"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2001,"doi":"10.1038/35102167","authors":"Reya T, Morrison SJ, Clarke MF, Weissman IL.","paperType":"review","findings":["Self-renewal pathways of normal stem cells (Wnt, Notch, Sonic hedgehog) are frequently deregulated in cancer.","In acute myeloid leukaemia only a rare, marker-defined subset of cells could transplant the disease into immunodeficient mice, the first experimental cancer stem cells.","Proposed that tumour growth and relapse are driven by cancer stem cells and that therapies should be judged by their effect on that population."],"whatItMeans":"The paper launched two decades of work on tumour-initiating cells in solid cancers, on why relapse follows apparently complete responses, and on measuring residual disease at the level of the cells that can regrow it. It also connected developmental biology pathways to cancer drug discovery.","caveats":["Whether cancer stem cells are a fixed population or a reversible cell state remains debated.","Transplantation assays in mice may select for cells that survive the assay rather than cells that drive the disease in patients."],"changedPractice":false},"route":"/key-papers/paper-reya-cancer-stem-cells-nature-2001/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"}],"institution":[{"id":"stanford","kind":"institution","name":"Stanford Health Care / Stanford Cancer Institute","route":"/institutions/stanford/"}],"term":[{"id":"cancer-stem-cell-theory","kind":"term","name":"Cancer stem cell theory and phenotypic plasticity","route":"/terms/cancer-stem-cell-theory/"},{"id":"relapse-recurrence","kind":"term","name":"Recurrence and relapse","route":"/terms/relapse-recurrence/"},{"id":"stem-cell","kind":"term","name":"Stem cell","route":"/terms/stem-cell/"}],"person":[{"id":"irving-weissman","kind":"person","name":"Irving L. Weissman","route":"/people/irving-weissman/"}],"paper":[{"id":"paper-al-hajj-breast-cancer-stem-cells-pnas-2003","kind":"paper","name":"Al-Hajj 2003: prospective identification of tumorigenic breast cancer cells","route":"/key-papers/paper-al-hajj-breast-cancer-stem-cells-pnas-2003/"},{"id":"paper-bao-glioma-stem-cells-radioresistance-nature-2006","kind":"paper","name":"Bao 2006: glioma stem cells resist radiotherapy by activating the DNA damage response","route":"/key-papers/paper-bao-glioma-stem-cells-radioresistance-nature-2006/"},{"id":"paper-singh-brain-tumour-initiating-cells-nature-2004","kind":"paper","name":"Singh 2004: identification of human brain tumour initiating cells","route":"/key-papers/paper-singh-brain-tumour-initiating-cells-nature-2004/"}]}}