Development of patient-derived models for pre-clinical studies in breast cancer
In collaboration with our clinical colleagues at the Huntsman Cancer Hospital, we have generated PDX (patient derived xenograft) and PDX organoid models of several subtypes of breast cancer that facilitates many avenues of cancer research. These models also allow testing of new drugs for breast cancer in vitro and in vivo, and should contribute to the evolution of functional precision medicine, whereby a patient could receive a treatment based on the specific phenotype, genotype, and drug responsiveness of their tumor. Please see our list of available models along with their general characteristics. PDX-derived organoids are also available for the lines indicated. More specific details for each model can be found here. Models are distributed through the HCI Preclinical Research Resource core. Please follow this process to request models:
- Request an MTA by sending an email to firstname.lastname@example.org and email@example.com
- Include a brief (few sentences) description of your planned work, for the MTA. You do not have to specify which models you want for this.
- Include contact information for your institution’s MTA office.
- Once the MTA is completed, contact the PRR to arrange model shipment: David.firstname.lastname@example.org
For more information on these models please see our publications:
- Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes
- Patient-derived models of human breast cancer: protocols for in vitro and in vivo applications in tumor biology and translational medicine
Mechanisms by which MSP promotes escape of metastatic cancer cells from the immune system
We are identifying the critical signals that mediate the macrophage:tumor cell interactions downstream of MSP and whether inhibition of the pathway can reduce or block metastasis in mouse models.
Mechanisms by which MSP preferentially induces metastasis to bone
We observed that MSP facilitates metastasis of breast cancer to bone and induces osteolysis, a common problem in human breast cancer. Our data suggest that MSP promotes bone metastasis by activating osteoclasts and causing bone resorption, which promotes further tumor growth. We are now identifying important downstream effectors of MSP that promote tumor growth in bone.
Pre-clinical studies of MSP inhibitors for treatment of metastatic breast cancer
Our studies showed that MSP not only promotes metastasis in mouse models of breast cancer, but also is significantly associated with metastasis and death in human breast cancer. We are currently testing inhibitors of the MSP signaling pathway in mouse models for efficacy in blocking or reducing metastasis. We are also testing these inhibitors on primary human breast cancer cells in patient-derived tumor grafts or xenografts (PDX).