Related Experiment Video

Updated: Nov 15, 2025

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
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Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

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Transcriptional mediators of treatment resistance in lethal prostate cancer

Meng Xiao He1,2,3, Michael S Cuoco3, Jett Crowdis2,3

  • 1Harvard Graduate Program in Biophysics, Boston, MA, USA.

Nature Medicine
|March 5, 2021
PubMed

Insights

Advanced prostate cancer cells show resistance mechanisms, including altered androgen receptor expression and signaling pathways. This study reveals insights into cancer and immune cell changes, guiding new therapeutic strategies.

Area of Science:

  • Oncology
  • Genomics
  • Immunology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is lethal, with resistance to therapies.
  • Mechanisms of resistance in cancer and immune cells are not well understood.

Purpose of the Study:

  • To characterize the transcriptional landscape of cancer and immune cells in advanced prostate cancer.
  • To identify cellular programs driving resistance to therapies.

Main Methods:

  • Single-cell RNA sequencing of tumor samples from 14 patients with advanced prostate cancer.
  • Analysis of gene expression in adenocarcinoma and small cell carcinoma cells, as well as CD8+ T cells.

Main Results:

  • Adenocarcinoma cells coexpressed multiple androgen receptor isoforms, potentially mediating therapy resistance.
  • Enzalutamide resistance linked to epithelial-mesenchymal transition and TGF-β signaling in cancer cells.
  • Small cell carcinoma cells showed distinct programs involving lineage plasticity and specific transcription factors (HOXB5, HOXB6, NR1D2).
  • A subset of patients displayed dysfunctional CD8+ T cells with clonal expansion after enzalutamide treatment.

Conclusions:

  • Transcriptional profiling provides insights into resistance mechanisms in mCRPC.
  • Findings support developing novel therapies that complement androgen signaling inhibition.

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