Targeting Breast Cancer Metastasis to Bone
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: Metastasis is the process through which cancer cells depart from the primary tumor to colonize and grow in distant organs. Metastatic spread is responsible for most breast cancer deaths. Despite advances in early detection and treatment, many patients who are treated for early stage breast cancer develop metastatic disease years later. This renders the concept of “cure” an unfulfilled promise for all breast cancer patients. Bone is the most common site of breast cancer metastasis and the presence of small numbers of cancer cells in the bone marrow at the time of diagnosis is linked to the later development of metastatic disease. Small numbers of breast cancer cells appear to travel to bone during the earliest stages of breast cancer development, and acquire properties that are different from the primary tumor that may resist treatment. Thus, even with advances in the early detection and treatment of primary tumors, we will never cure breast cancer without creating better methods to target cancer cells lurking within the bone metastatic niche. 
 
 
 
 
 
 
 
 The question(s) or central hypotheses of the research: 
 
 The goal of this grant is to use small human bone tissue fragments in culture dishes as a model system for testing therapies to prevent and treat breast cancer metastasis to bone. We predict that we can measure the response of breast cancer cells to treatment as they grow within the bone tissues. 
 
 
 
 
 
 
 
 The general methodology:
 
 We will isolate breast cancer cells from fresh human breast tumor tissues obtained from breast cancer patients undergoing surgery at Stanford, and then categorize them for the presence of two common treatment targets: ER (estrogen receptor), which is treated with tamoxifen, and Her-2, which is treated with Herceptin. Next we will transfer the ER and Her-2 breast cancer cells into small bone tissue fragments isolated from human hip replacement surgeries. We will then track the growth of the breast cancer cells within the bone tissues during treatment with tamoxifen and Herceptin. Showing that we can measure known targets during treatment with current drugs will prove that our model can be used to test new, more effective approaches to prevent and treat breast cancer metastasis to bone. 
 
 
 
 
 
 
 
 Innovative elements of the project:
 
 Breast cancer metastasis is usually studied in mice, but these experiments take many weeks or months, and human breast cells do not always grow well in the mouse skeleton. In addition, it is difficult to study specific breast cancer cell responses within the bone tissues of a mouse. We have developed a new culture system in which human breast cancer cells are grown in small human bone tissue fragments. We are using new methods to isolate and categorize breast cancer cells from primary tumors so that we can study how their properties and behavior change once they start to grow in the bone tissues. And finally, we can treat the breast cancer cells within this “metastatic niche” and measure responses within a matter of days to determine if, and how a drug is working.
 
 
 
 
 
 
 
 Publications: 
 
 
 
 Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells