Cancer treatment with endothelin receptor antagonists

摘要

The present invention relates to therapeutic protocols and pharmaceutical compositions designed to treat and prevent cancer. More specifically the present invention relates to a novel method of treating cancer using antagonists to the endothelin B receptor (ETB) or inactive mimic forms of endothelin-1. The pharmaceutical compositions of the invention are capable of selectively inhibiting the early events associated with the development of cancer. The present invention further relates to screening assays to identify compounds which inhibit ETB activation.

主权项

1. A method for inhibiting the early development of mammary cancer in a patient in need thereof, comprising administering a therapeutically effective amount of a selective endothelin B receptor ETB antagonist to said patient, with the proviso that said method does not include gene therapy, wherein said antagonist does not include sRNA, antisense molecules and ribozymes, and wherein the ability of the selective endothelin B receptor (ETB) antagonist to antagonize the endothelin B receptor (ETB) is determined in vitro by:
a. contacting a cell culture expressing endothelin B receptor (ETB) and E-cadherin with endothelin and a selective ETB antagonist; b. determining the level of E-cadherin expression; and c. comparing the level of E-cadherin expression determined in step b) to that of a control culture in the absence of the selective ETB antagonist, so that an increase in expression of E-cadherin indicates antagonist activity.