AT4 receptor ligands as angiogenic, anti-angiogenic, and anti-tumor agents

Abstract

AT4 receptor agonists are potent activators of angiogenesis and can be used to treat diseases that are characterized by vascular insufficiency. AT4 receptor antagonists, which are potent inhibitors of angiogenesis, and can be used as anti-angiogenic agents for the treatment of cancer, diabetic retinopathy, rheumatoid arthritis, psoriasis, atherosclerotic plaque formation, and any disease process that is characterized by excessive, undesired or inappropriate angiogenesis or proliferation of endothelial cells.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application is a continuation of U.S. patent application Ser. No. 10 / 675,470, filed Sep. 30, 2003, now pending, which application is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention relates to the general utility of AT4 receptor ligands to alter blood vessel growth (angiogenesis) in diseases associated with insufficient blood supply or those associated with excessive, undesired or inappropriate angiogenesis or proliferation of endothelial cells. In particular, AT4 receptor ligands that inhibit angiogenesis are extremely potent anti-cancer agents that block both the growth of primary tumors and the development of metastatic tumors. [0004] 2. Description of Related Art [0005] The dominant therapeutic approaches that are currently employed to treat cancer include surgical removal of primary tumors, tumor irradiation, and parenteral application of ...

AI Technical Summary

Problems solved by technology

The continued dominance of these long established therapies is mirrored by the lack of improvement in survival rates for most cancers.

In addition to limited clinical success, devastating side effects accompany classic therapies.

Both radiation- and cytotoxic-based therapies result in the destruction of rapidly dividing hematopoietic and intestinal epithelial cells leading to compromised immune function, anemia, and impaired nutrient absorption.

Their removal, without accompanying treatment that is directed at the micrometastases often leads to rapid expansion of the metastatic tumors with fatal consequences.

Although, the vaccine and immunotoxin therapeutic approach has been under development for some time no immuno-based therapy is now in use as a standard cancer treatment.

The utility of this approach is limited by two properties that are inherent to cancer cells.

Therefore, each cancer type would necessarily require its own specific set of therapeutic reagents that would entail prohibitively expensive individual development.

Second, the antigenic targets of the reagents would never be totally unique to the transformed cancer cells but would also be represented on normal healthy cells resulting in unwanted cytotoxic damage.

Hormone-based therapies, while useful for the treatment of a select group of cancers, will never be a treatment option that is generally applicable to the vast majority of cancers that are hormone insensitive.

Without a dedicated blood supply the availability of nutrients and oxygen, which must be furnished by vessels external to the neoplasm, is diffusion limited restricting tumor size to about 1 millimeter in diameter.

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