Novel Postpartum Liver Biology Has Implications for Breast Cancer Liver Metastasis
Technical Report,15 Mar 2018,14 Mar 2019
Oregon Health and Science University Portland United States
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The poor prognosis of young women diagnosed with BrCa is highest in women diagnosed postpartum, up to 10 years out from a completed pregnancy. Our newer data show that this poor prognosis can be tracked to increased liver metastasis data that argues strongly for the development of treatments that are effective at blocking metastatic lesions in the liver. Recently, the concept of targeting the metastatic cell niche has gained momentum. However, this approach is seriously hampered by difficulties in finding and characterizing disseminated tumor cells. Here we tackle the problem of defining the liver-BrCa tumor cell niche in models of postpartum breast cancer and explore relevance to women, laying the foundation for rational drug design to treat metastatic BrCa to the liver. ObjectiveSpecific Aims We identify the lack of understanding of postpartum liver biology as a major obstacle to identifying therapeutic targets aimed at destabilizing the liver metastatic niche in postpartum breast cancer patients. To advance this goal, mechanistic studies and stronger translational rationale are needed. To fill these critical gaps, we propose the following Aim 1 Use liver metastasis mouse models to decipher the post-intravasation steps of the metastatic cascade that are supported by the involuting liver. Aim 2 Explore the liver metastatic niche in breast cancer patients utilizing tumor and adjacent normal liver tissue obtained from breast cancer patients with liver metastases. Aim 3 Obtain first-of-kind evidence for weaning-induced liver involution in women via a serial MRI imaging study of livers in healthy women across pregnancy and weaning.
- Medicine and Medical Research
- Anatomy and Physiology