Manipulating the angiotensin system--new approaches to the treatment of solid tumours.
Angiotensin II (Ang II), a main effector peptide in the renin-angiotensin system (RAS), plays a fundamental role as a vasoconstrictor in controlling cardiovascular function and renal homeostasis. Ang II also acts as a growth promoter or angiogenic factor via type 1 angiotensin II receptors (AT1Rs) in certain tumour cell lines. Recent studies have shown the activation of the local RAS in various tumour tissues, including the abundant generation of Ang II by angiotensin-converting enzyme (ACE) and the upregulation of AT1R expression. Thus, considerable attention has been paid to the role of the RAS in cancer and its blockade as a new approach to the treatment of cancer. There is increasing evidence that the Ang II-AT1R system is involved in tumour growth, angiogenesis and metastasis in experimental models, suggesting the therapeutic potential of an ACE inhibitor and AT1R blocker, both of which have been used as antihypertensive drugs. In addition, specific Ang II-degrading enzymes are expressed in tumours and play a regulatory role in cell proliferation and invasion. This review focuses on the role of the Ang II-AT1R system in solid tumours, particularly in the progression of gynaecological cancer, and presents the clinical potential of manipulating the angiotensin system as a novel and promising strategy for cancer treatment.
Ino
Kazuhiko
K
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. kazuino@med.nagoya-u.ac.jp
Shibata
Kiyosumi
K
Kajiyama
Hiroaki
H
Nawa
Akihiro
A
Nomura
Seiji
S
Kikkawa
Fumitaka
F
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000809:Angiotensins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D000970:Antineoplastic Agents