[Renin-angiotensin system and urological cancers].
BACKGROUND
A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers.


METHODS
We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting.


RESULTS
Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers.


CONCLUSIONS
Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings.
Service d'urologie, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes, France; CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France. Electronic address: gregory.verhoest@chu-rennes.fr.
G
G
Verhoest
CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France; Service de néphrologie, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes, France.
T
T
Dolley-Hitze
CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France.
F
F
Jouan
Service d'urologie, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes, France.
K
K
Bensalah
CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France.
Y
Y
Arlot-Bonnemains
CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France; Service de cytogénétique, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes, France.
F
F
Dugay
CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France; Service de cytogénétique, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes, France.
M-A
MA
Belaud-Rotureau
CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France; Service d'anatomie et cytologie pathologiques, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes, France.
N
N
Rioux-Leclercq
CNRS UMR6290/Biosit, faculté de médecine, université Rennes 1, 2, avenue du Professeur-Léon-Bernard, CS 34317, 35043 Rennes cedex, France; Service de néphrologie, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35033 Rennes, France.
C
C
Vigneau
D006801:Humans; D012084:Renin-Angiotensin System / Q000502:physiology*; D014571:Urologic Neoplasms / Q000209:etiology*
AT1R; Angiogenesis; Angiogénèse; Antagonistes des récepteurs de l’Angiotensine II; Antagonists of angiotensin-II receptors; Inhibiteurs de l’enzyme de conversion; Inhibitors of angiotensinogen converting enzyme; VEGF