Awakening the sleeping beauty: towards a better understanding of cancer cell dormancy

Breast cancer (BC) is the leading cancer diagnosed among women in the world. A large range of therapies is currently available, however, the inability to treat metastasis, one of the main sources of cancer-related death, is now a major challenge faced by oncologists. Metastasis is linked to tumor cell dormancy, a state in which cells do not cycle and are resistant to chemotherapy. Between 36-56% of BC patients have dormant cells in their bone marrow that can potentially relapse and form metastases at any time. This poses tumor cell dormancy as a major clinical problem. We aim to understand the mechanisms that govern tumor cell dormancy by using a variety of single cell technologies.

TGF-β inhibitors have produced mixed results in clinical trials with metastatic melanoma patients. Most metastatic melanoma patients diagnosed with liver metastases still die within months after diagnosis. Thus, treatments must be improved. To do so, we are interested in increasing our insights into how TGF-β signaling regulates hepatic colonization of metastatic melanoma cells. TGF-β regulates a variety of processes during metastasis including tumor cell intrinsic processes like cell migration and proliferation, but also tumor microenvironmental processes like activation of CAFs and the regulation of inflammation. Specific interplay between these processes most likely determines successful hepatic colonization of metastatic melanoma cells. We are investigating the spatiotemporal patterns of TGF-β signaling in tumor and microenvironmental cells during melanoma metastasis using unique advanced in vivo microscopy techniques. A detailed dissection of this process will likely guide us towards improved TGF-β blocking strategies by targeting specific cells and/or during specific colonization time windows. In addition, we are investigating whether immune checkpoint inhibitors, currently used to treat metastatic melanoma patients, can be combined with TGF-β inhibitors to improve treatment of metastatic melanoma patients. Ultimately, this will inform us on how to better use TGF-β inhibitors to treat melanoma liver metastases.


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