Reya 2001: stem cells, cancer and cancer stem cells
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.
Overview
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.
- 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.
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.
- 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.
This paper connected the cancer stem cell idea to a clinical problem, the near-universal recurrence of glioblastoma after radiotherapy, and gave a mechanism and a drug target. It is part of the rationale for combining radiotherapy with DNA damage response inhibitors now in trials.
This paper extended the cancer stem cell concept from leukaemia to a common solid tumour and started the search for tumour-initiating cells across cancers. It underpins research on why cancers relapse after treatments that shrink them and on therapies aimed at the cells that regrow disease.
Similar pages
not linked directly; found by shared links- TreatmentMagrolimab
- TargetCD47
Shares Irving L. Weissman, Stanford Health Care / Stanford Cancer Institute, Acute myeloid leukaemia.
- PathwayHedgehog signalling
Shares Stanford Health Care / Stanford Cancer Institute, Acute myeloid leukaemia.
- PathwayTumour dormancy
Shares Recurrence and relapse, Stem cell.
- PathwayCancer stem cells & phenotypic plasticity
Shares Stem cell, Stanford Health Care / Stanford Cancer Institute.
- TermLeukaemia (tissue type)
Shares Stem cell, Acute myeloid leukaemia.