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Some cancer cells behave like stem cells: they can regrow the whole tumour, resist treatment, and switch identities. This plasticity explains why tumours come back and why some lung and prostate cancers transform into a different cancer type under therapy.
Cancer stem cells (CSCs; first shown in AML by Dick, 1994-97) are functionally defined by tumour-initiating capacity; in solid tumours stemness is usually a reversible state rather than a fixed population. Lineage plasticity under therapy produces neuroendocrine transformation (EGFR-mutant NSCLC to SCLC; prostate adenocarcinoma to NEPC), basal/mesenchymal switching in breast cancer, and dedifferentiation. Drivers: EMT programmes, Wnt/Notch/Hedgehog, epigenetic remodelling (EZH2, SWI/SNF), TP53/RB1 loss. 'Unlocking phenotypic plasticity' is a 2022 hallmark. Therapeutic routes: differentiation therapy (ATRA in APL), EZH2/LSD1 inhibitors, targeting CSC markers (CD44, LGR5), and MRD-directed therapy.
A weed that can turn from leaf to root to seed depending on what you spray on it. Kill the leaves and the roots wait; kill the roots and a seed reawakens.
Cancer is now understood to change its identity and behaviour without new mutations, to be shaped by bacteria inside and around it, and to be helped along by ageing cells. This explains why some tumours escape targeted drugs by changing cell type and why gut bacteria affect immunotherapy response.
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A mechanism for the most feared form of treatment resistance in prostate cancer, and the reason combined TP53 and RB1 loss is worth knowing about before a man starts an androgen receptor drug rather than after his biopsy comes back neuroendocrine. Reversibility in the laboratory is also an argument that the switch is a target and not just a prognosis.
It made TGF-beta the central target of the microsatellite-stable half of the disease, which is the line that leads to Tauriello's immune-evasion work and to the TGF-beta plus checkpoint combinations 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.
Shares Drug-tolerant persister cells, Stanford Health Care / Stanford Cancer Institute, Epithelial-mesenchymal transition & drug efflux, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares The Francis Crick Institute, Theories of cancer: how the ideas connect, Stanford Health Care / Stanford Cancer Institute, Clonal evolution & minimal residual disease and the tag mechanism.
Shares Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells, Drug-tolerant persister cells, Memorial Sloan Kettering Cancer Center, TP53 and the tag mechanism.
Shares The Francis Crick Institute, Theories of cancer: how the ideas connect, Clonal evolution & minimal residual disease, Epigenetic reprogramming and the tag mechanism.
Shares Theories of cancer: how the ideas connect, Clonal evolution & minimal residual disease, Epigenetic reprogramming, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares The Francis Crick Institute, Epithelial-mesenchymal transition & drug efflux, Clonal evolution & minimal residual disease, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Stem cell, Clonal evolution & minimal residual disease, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares SWI/SNF chromatin remodelling, The Francis Crick Institute, TP53 and the tag mechanism.