Convergent evolution of complex structural variants drives therapy resistance in metastatic prostate cancer
Cancer resistance patterns circulating in blood can be detected early, offering doctors a way to monitor therapy response without repeated biopsies.
A comprehensive genomic study of 193 mCRPC tumors with matched Hi-C data reveals that extrachromosomal DNA and complex structural variants amplifying AR and MYC are pervasive drivers of therapy resistance, arising via convergent evolution in independent tumor sites within a single patient. Importantly, these resistance-driving cSVs are detectable in circulating tumor DNA, enabling non-invasive monitoring.
What the study was
- Study design
- Retrospective WGS + transcriptome + Hi-C cohort study with rapid autopsy substudy
- Population
- Metastatic castration-resistant prostate cancer (mCRPC) patients
- Sample size
- 193
- Category
- Genomics/Precision Medicine
- Maturity
- Validated
- Journal
- Genome Biology
Why it surfaced
Largest ecDNA/cSV characterization in mCRPC to date (n=193 + 53 rapid autopsy samples); identifies convergent evolution as a key resistance mechanism and demonstrates ctDNA detectability, enabling rational future trial design to intercept resistance early.
A plain-language summary of published research — not medical advice. Talk to a clinician about your own care.