Novel Anti-Angiogenic Agents for Breast Cancer Therapy
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Solid human tumors, such as breast cancers, cannot continue growing without an adequate network of blood vessels from normal tissue to supply oxygen and nutrients and to remove waste products. When a breast tumor reaches a size (generally 1-2 mm in diameter) that overwhelms the ability of its blood supply to support further growth, stressful microenvironments develop within the tumor. This results both in the rise of new and more aggressive cancer cells and the generation of some of the signals necessary for the growth of new blood vessels (angiogenesis) to support further tumor growth. Angiogenesis is essential for the survival and further progression of breast cancers to full malignancy. However, although composed of normal cells (endothelial cells), tumor blood vessels are structurally and functionally very different from blood vessels formed in normal tissues. These properties contribute to the "immature" and sensitive nature of tumor vascular lining and make it an attractive target for therapy. We propose to develop a compound we recently discovered that inhibits growth of both breast tumor cells and acts specifically on tumor blood vessels. 
 
 
 
 
 
 
 
 Recent research has shown that tumor blood vessels can be targeted for disruption by a class of drug under intense development for the treatment of hormonally responsive breast tumors, called selective estrogen receptor modulators (SERMs). Tamoxifen is an example of a clinically important SERM that can inhibit the growth and survival of tumor blood vessels, but it has side effects, such as the risk of uterine cancer. We will use the CBCRP funding to investigate a new SERM (called SR 16234). This drug inhibits tumor cell proliferation and suppresses the growth of human breast implants in mice with remarkably little normal tissue toxicity. Preliminary studies show that it also inhibits the proliferation of human blood vessel cells and antagonizes the formation of new blood vessels in a non-breast cancer assay. Our novel SERM has ideal characteristics for treating advanced breast cancer: oral administration, little normal tissue toxicity, safety toward estrogen-responsive normal tissues, and inhibition of both tumor cell growth and angiogenesis. We propose to clearly establish the role and effectiveness of SR 16234 in inhibiting proliferating blood vessel cells both in cell culture and in animal models of human breast cancer. Such pre-clinical information is essential for determining the value of SR 16234 as an experimental drug for breast cancer therapy.
 
 
 
 
 
 
 
 The combination of anti-angiogenesis and SERM activity has special advantages for treating breast cancer. A pure anti-angiogenic agent that doesn’t target tumor cells might only serve to arrest tumor growth for a short time until the development of drug resistance. In addition, the SERM/anti-angiogenic approach has the potential to treat both the primary breast tumor and distant metastatic sites (e.g., bone, lung, liver), which are the eventual cause of mortality.