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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.
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.
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.
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 model to brain tumours and set up the later finding that these cells resist radiotherapy. It is the basis for treatment strategies aimed at the cells that regrow glioblastoma after surgery and chemoradiation.
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.
Shares Al-Hajj 2003: prospective identification of tumorigenic breast cancer cells, Stem cell.
Shares Cancer stem cell theory and phenotypic plasticity, Acute myeloid leukaemia.
Shares Singh 2004: identification of human brain tumour initiating cells, Stem cell, Cancer stem cell theory and phenotypic plasticity, Stanford Health Care / Stanford Cancer Institute.
Shares Irving L. Weissman, Stanford Health Care / Stanford Cancer Institute, Acute myeloid leukaemia.
Shares Cancer stem cell theory and phenotypic plasticity, Stanford Health Care / Stanford Cancer Institute, Acute myeloid leukaemia.
Shares Stem cell, Recurrence and relapse.
Shares Stem cell, Acute myeloid leukaemia.