# Detect tumours changing cell type from RNA in the blood

Source: https://onco.cc/ideas/idea-bio1-cfrna-plasticity-tracking/  
OnCo record `idea-bio1-cfrna-plasticity-tracking` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- roadmaps: [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](https://onco.cc/roadmaps/prostate-roadmap/)
- ideas: [Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it](https://onco.cc/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [DLL3](https://onco.cc/targets/dll3/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Tarlatamab](https://onco.cc/drugs/tarlatamab/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- key papers: [SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer](https://onco.cc/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/), [Vogelstein, Lane and Levine 2000: surfing the p53 network](https://onco.cc/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/)

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