Uncovering the Coevolution of the Microenvironment in Breast Cancer Metastasis: Toward Discovery of Novel Therapeutic Targets
Abstract
Mortality from breast cancer is almost exclusively a result of tumor metastasis to distant organs. Metastatic cancers are mostly incurable, and available therapies can only prolong life to a limited extent. In breast cancer, there is very often a long temporal gap between surgical removal of the primary tumor, followed by radiotherapy and/or chemotherapy, and the emergence of metastatic disease. However, in patients that experience metastatic relapse, disseminated cancer cells have reached the distant site prior to diagnosis, and remained undetected as micrometastases for months/years, because of limitations in diagnostics and imaging tools available today. Therefore, the early stages of metastasis are in fact a “black box.” Our research will address the overarching challenge of eliminating mortality from breast cancer metastasis, by uncovering the early changes that enable breast cancer metastatic relapse. Extensive research in the last decades has led to the understanding that tumors are more than a collection of cancer cells and that cells in the tumor microenvironment (including immune cells, cells of connective tissue, and blood vessels) play a central role in all stages of cancer progression. Nevertheless, changes in the microenvironment of distant organs in which metastases occur, which enable cancer cells to grow in the hostile microenvironment of distant organs, are still poorly characterized. Our goal is to uncover the pathways that mediate these changes and contribute to the formation of breast cancer lung and bone metastases. To that end, we will investigate in detail the changes in accessory cells in lung and bone metastasis by dissecting their different subpopulations at the single cell level and uncover the pathways that create a hospitable microenvironment for metastasizing breast cancer cells. Understanding the dynamic changes in the metastatic microenvironment that precede and facilitate metastasis will enable the discovery of novel target molecules for therapeutics. By the end of this study, we hope to have several candidate molecules that can be tested preclinically, followed by clinical evaluation of their efficiency in preventing metastatic relapse of breast cancer. Our vision is that the knowledge from our study will enable therapeutic approaches that will be able to prevent, rather than try to cure, breast cancer metastases, thus transforming cancer into a chronic, yet manageable disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110395
Entities
People
- Ido Amit
Organizations
- United States Army
- Weizmann Institute of Science