Therapeutic angiogenesis: hope or hype.

Abstract

To the Editor: Grines et al1 assert that the vascular endothelium and/or the myocardium can incorporate a human, replication-deficient adenovirus vector (Ad5-FGF4) in which one gene is replaced with the human FGF4 gene that is delivered by intracoronary infusion. This, according to the authors, allows sustained in situ production of “angiogenic growth factors.” The data show, however, that the vector was detected in the pulmonary artery and later in the venous blood. Thus, the alleged lack of systemic exposure to the unidentified growth factors is not convincing. The observation that 2 patients (3%) were diagnosed with malignancies 69 days (brain) and 267 days (colon) after the treatment was dismissed as unrelated occurrences. Furthermore, the report does not discuss the more general angiogenesis-neoplasia link, described initially nearly 100 years ago. In 1971, Folkman advanced the now well accepted postulate that tumor growth and metastasis are angiogenesis-dependent, and hence blocking angiogenesis could be an effective strategy to arrest tumor proliferation.2 Not surprisingly, in 2000, …