There is significant evidence that both
angiotensin I converting enzyme inhibitors (ACEI) and type 1 and type 2
angiotensin 2 (A2) receptor blockers may inhibit
tumor growth. The finding is supported by many reports where these two classes of drugs showed
cytostatic effects on the cultures of several lines of both normal and neoplastic cells. These drugs often transformed the cellular biochemical structures, especially in neoplastic cell lines. The same drugs also delayed the growth of different types of
tumors in a variety of experimental animals (breast and lung
carcinoma in mice;
sarcomas,
squamous cell carcinomas and
hepatocellular carcinomas in rats), and there are a few reports of successful treatment of a limited number of cases of
Kaposi sarcoma and
gliomas with these drugs. Retrospective studies in hypertensive subjects treated with ACEI or A2 receptor blockers also seem to indicate that the incidence and growth of different
neoplasms was delayed when these patients were compared to hypertensive patients receiving alternate medications. There is strong indication that the pharmacologic effect of these drugs may be exerted by reduction or inhibition of the synthesis of
angiotensin 2. A2 is a powerful
mitogen and its effect on cellular growth is exerted through stimulation of many factors, including
transforming growth factor beta (
TGFbeta),
epidermal growth factor (
EGF), smooth muscle actin (SMA), and
tyrosine kinase. A2 also regulates apoptotic mechanisms and angiogenesis. The
pharmacologic action of most of these drugs, however, is not necessarily limited to downregulaton of A2. Many ACEI, especially those containing the sulfhydryl (SH group), possess
antioxidant or
metalloprotease inhibitory properties per se. These experimental and retrospective data justify clinical testing of these drugs in appropriate randomized trials. Several such trials are currently in process. If these trials confirm the experimental and retrospective studies, these agents will provide a significant contribution to the therapeutic treatment of many
malignancies in humans.