{"entity":{"id":"idea-bio1-cfrna-plasticity-tracking","kind":"idea","name":"Detect tumours changing cell type from RNA in the blood","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":["prostate-roadmap","idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine"],"cancers":["nsclc","prostate","sclc"],"sections":[],"technologies":["liquid-biopsy","rna-seq"],"targets":["dll3","tp53"],"drugs":["tarlatamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A plasma-derived lineage score rises at least three months before histological confirmation of neuroendocrine transformation and enables an earlier treatment switch that improves survival in this subgroup.","rationale":"Transformation is frequent in RB1/TP53-altered EGFR-mutant and castration-resistant disease; cfDNA fragmentomics has already discriminated neuroendocrine from adenocarcinoma prostate cancer in small studies.","test":"Serial plasma in 200 RB1/TP53-altered patients on TKI or androgen-receptor therapy, blinded scoring, comparison with clinically indicated biopsies.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-cfrna-plasticity-tracking/","neighbours":{"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/prostate-roadmap/"}],"idea":[{"id":"idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine","kind":"idea","name":"Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it","route":"/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"dll3","kind":"target","name":"DLL3","route":"/targets/dll3/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","route":"/drugs/tarlatamab/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"paper":[{"id":"paper-mu-sox2-lineage-plasticity-science-2017","kind":"paper","name":"SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer","route":"/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/"},{"id":"paper-vogelstein-surfing-p53-network-nature-2000","kind":"paper","name":"Vogelstein, Lane and Levine 2000: surfing the p53 network","route":"/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/"}]}}