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Divergent Clonal Evolution and Early Dissemination Promote Genetic Heterogeneity of Metastases in Castration-Resistant Prostate Cancer.

Cancer research - 3 Nov 2025

Hosseini Noshad, Mannan Rahul, Rebernick Ryan J, Su Fengyun, Wang Rui, Cao Xuhong, Lako Ana, Mellacheruvu Dattatreya, Hu Jing, Alumkal Joshi J, Reichert Zachery R, Malik Rohit, Mehra Rohit, Chinnaiyan Arul M, Cieslik Marcin P

Abstract excerpt

Lethal prostate cancer has passed through at least two evolutionary bottlenecks: acquisition of metastatic potential and development of castration resistance. A better understanding of how this affects genetic heterogeneity across metastatic sites is needed to develop strategies to block metastatic spread and to overcome resistance. By leveraging deep whole-exome sequencing of 93 tumors from 26 patients, we...

Topics

Humans
Male
Prostatic Neoplasms, Castration-Resistant
Clonal Evolution
Genetic Heterogeneity
Neoplasm Metastasis
Mutation
Exome Sequencing
DNA Copy Number Variations

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PMID: 40824681
DOI: 10.1158/0008-5472.CAN-24-3687
PMCID: PMC12580794

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