Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer

Joakin O. Mori, Isra Elhussin, W. Nathaniel Brennen, Mindy K. Graham, Tamara L. Lotan, Clayton C. Yates, Angelo M. De Marzo, Samuel R. Denmeade, Srinivasan Yegnasubramanian, William G. Nelson, Gerald V. Denis, Elizabeth A. Platz, Alan K. Meeker, Christopher M. Heaphy*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

Original languageEnglish (US)
Pages (from-to)258-273
Number of pages16
JournalNature Reviews Urology
Volume21
Issue number5
DOIs
StatePublished - May 2024

ASJC Scopus subject areas

  • Urology

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