Integrating new discoveries into the "vicious cycle" paradigm of prostate to bone metastases

Leah M. Cook, Gemma Shay, Arturo Aruajo, Conor C. Lynch

Research output: Contribution to journalReview articlepeer-review

59 Scopus citations


In prostate to bone metastases, the "vicious cycle" paradigm has been traditionally used to illustrate how metastases manipulate the bone forming osteoblasts and resorbing osteoclasts in order to yield factors that facilitate growth and establishment. However, recent advances have illustrated that the cycle is far more complex than this simple interpretation. In this review, we will discuss the role of exosomes and hematopoietic/mesenchymal stem/stromal cells (MSC) that facilitate the establishment and activation of prostate metastases and how cells including myeloid-derived suppressor cells, macrophages, T cells, and nerve cells contribute to the momentum of the vicious cycle. The increased complexity of the tumor-bone microenvironment requires a system level approach. The evolution of computational models to interrogate the tumor-bone microenvironment is also discussed, and the application of this integrated approach should allow for the development of effective therapies to treat and cure prostate to bone metastases.

Original languageEnglish (US)
Pages (from-to)511-525
Number of pages15
JournalCancer and Metastasis Reviews
Issue number2-3
StatePublished - Sep 2014
Externally publishedYes


  • Bone metastasis
  • Immune cells
  • Mathematical modeling
  • Prostate cancer
  • Stem cells
  • Vicious cycle

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Integrating new discoveries into the "vicious cycle" paradigm of prostate to bone metastases'. Together they form a unique fingerprint.

Cite this