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Some cancers escape treatment by changing into a different kind of cell that the drug no longer affects. Tumour RNA in blood could show this shift months before a biopsy would.
Lineage plasticity (adenocarcinoma to small cell or neuroendocrine transformation in EGFR-mutant lung and prostate cancer) is a DNA-invisible resistance mechanism, usually diagnosed by biopsy late. Cell-free RNA and nucleosome footprinting can infer transcriptional state from plasma. The proposal is a plasma neuroendocrine transformation score monitored in patients at genetic risk (RB1 and TP53 loss) so that the switch to platinum-etoposide or a DLL3 bispecific is made early.
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.
This paper is the reason TP53 status, MDM2 amplification and CDKN2A loss are read together in tumour genomes. It frames the current drug development around MDM2 inhibitors and mutant p53 reactivators as attempts to restore a network rather than a single protein.
Shares SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Prostate cancer.
Shares Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it, Acquired resistance to every therapy, Liquid biopsy (ctDNA), Small-cell lung cancer.
Shares SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it, Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy.
Shares Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy, Liquid biopsy (ctDNA), Non-small-cell lung cancer.
Shares DLL3, Tarlatamab, Small-cell lung cancer.
Shares SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it.
Shares SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, TP53.
Shares Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy, Liquid biopsy (ctDNA), Non-small-cell lung cancer.