Screening for liver X receptor modulators: Where are we and for what use? - Université Clermont Auvergne Access content directly
Journal Articles British Journal of Pharmacology Year : 2021

Screening for liver X receptor modulators: Where are we and for what use?

Julio Buñay
Allan Fouache
  • Function : Author
Amalia Trousson
Erwan Bouchareb
  • Function : Author
Zhekun Zhu
  • Function : Author
Ayhan Kocer
  • Function : Author
Laurent Morel
Silvère Baron
Jean‐marc Lobaccaro


Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.
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Dates and versions

hal-04028131 , version 1 (14-03-2023)



Julio Buñay, Allan Fouache, Amalia Trousson, Cyrille de Joussineau, Erwan Bouchareb, et al.. Screening for liver X receptor modulators: Where are we and for what use?. British Journal of Pharmacology, 2021, 178 (16), pp.3277-3293. ⟨10.1111/bph.15286⟩. ⟨hal-04028131⟩
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