Angiotensin Peptides and Cancer

Tallant, E. Ann; Menon, Jyotsana; Soto-Pantoja, David R.; Gallagher, Patricia E.

doi:10.1016/b978-012369442-3/50069-6

Cited by 2 publications

(3 citation statements)

References 44 publications

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“…This phase I trial validates the renin-angiotensin system as a target for cancer therapy (25-27). All of the necessary prohormones, peptidases, and receptors are found in cancers (27, 28), as shown in Fig.…”

Section: Discussionmentioning

confidence: 61%

Phase I and Pharmacokinetic Study of Angiotensin-(1-7), an Endogenous Antiangiogenic Hormone

Petty

Miller

McCoy

et al. 2009

Clinical Cancer Research

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Purpose Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide hormone of the reninangiotensin system with antiproliferative and antiangiogenic properties. The primary objective of this study was to establish the recommended phase II dose of Ang-(1-7) for treating patients with advanced cancer. Secondary objectives were to assess toxicities, pharmacokinetics, clinical activity, and plasma biomarkers. Experimental Design Patients with advanced solid tumors refractory to standard therapy were treated with escalating doses of Ang-(1-7) in cohorts of three patients. Ang-(1-7) was administered by s.c. injection once daily for 5 days on a 3-week cycle. Tumor measurements were done every two cycles and treatment was continued until disease progression or unacceptable toxicity. Results Eighteen patients were enrolled. Dose-limiting toxicities encountered at the 700 μg/kg dose included stroke (grade 4) and reversible cranial neuropathy (grade 3). Other toxicities were generally mild. One patient developed a 19% reduction in tumor measurements. Three additional patients showed clinical benefit with stabilization of disease lasting more than 3 months. On day 1, Ang-(1-7) administration led to a decrease in plasma placental growth factor (PlGF) levels in patients with clinical benefit (P = 0.04) but not in patients without clinical benefit (P = 0.25). On day 5, PlGF levels remained lower in patients with clinical benefit compared with patients without clinical benefit (P = 0.04). Conclusions Ang-(1-7) is a first-in-class antiangiogenic drug with activity for treating cancer that is linked to reduction of plasma PlGF levels. The recommended phase II dose is 400 μg/kg for this administration schedule.

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Section: Discussionmentioning

confidence: 61%

Phase I and Pharmacokinetic Study of Angiotensin-(1-7), an Endogenous Antiangiogenic Hormone

Petty

Miller

McCoy

et al. 2009

Clinical Cancer Research

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“…The RAS is a physiological regulator of blood pressure, homeostasis, and cell proliferation, as reviewed in [5-8]. The parent compound angiotensinogen, produced predominantly in the liver and secreted into the circulation, is degraded by circulating renin to the decapeptide angiotensin I (Ang I), as shown in Fig.…”

Section: The Rasmentioning

confidence: 99%

“…A functional tissue RAS was identified in every organ and tissue investigated, although some components of the pathway, particularly renin, are not always synthesized locally but are acquired from the endocrine RAS. In addition to normal tissues, RAS components are expressed in a variety of tumor cells, including carcinomas of the bladder, brain, cervix, colon, kidney, liver, lung, pancreas, prostate, skin, and stomach as previously reviewed [5, 36-38] as well as additional articles in this issue. The RAS as a chemotherapeutic target for cancer garnered attention in recent years since Ang II is implicated in cell proliferation and migration, angiogenesis, inflammation, and extracellular matrix formation.…”

Section: The Rasmentioning

confidence: 99%

Angiotensin Peptides and Lung Cancer

Gallagher¹,

Cook²,

Soto-Pantoja³

et al. 2011

CCDT

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Lung cancer is a leading cause of death in both men and women, with over 1,000,000 new cases diagnosed worldwide annually and a 5-year survival rate of only 14%, a figure that has improved little in the past thirty years. This poor prognosis suggests a need for novel approaches for the treatment and prevention of lung cancer. The renin-angiotensin system is an established, primary regulator of blood pressure, homeostasis, and natriuresis; however, compelling evidence indicates that the angiotensin peptides also play a role in cell proliferation and inflammation. Angiotensin II is a vasoconstrictor, a mitogen, and an angiogenic factor, while angiotensin-(1-7) has vasodilator, anti-proliferative, and anti-angiogenic properties. This review focuses on studies examining the renin-angiotensin system in pulmonary cancers and whether clinical intervention of this pathway may serve as an effective chemotherapeutic and/or chemopreventive modality for lung cancer.

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Angiotensin Peptides and Cancer

Cited by 2 publications

References 44 publications

Phase I and Pharmacokinetic Study of Angiotensin-(1-7), an Endogenous Antiangiogenic Hormone

Phase I and Pharmacokinetic Study of Angiotensin-(1-7), an Endogenous Antiangiogenic Hormone

Angiotensin Peptides and Lung Cancer

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