Tackling Triple negative breast cancer Research by Investigating Uncharted Metastatic Pathways and microenvironments for Hope – TRIUMPH

Triple-negative breast cancer (TNBC) is an aggressive subtype marked by early metastatic recurrence and resistance to chemotherapy. Understanding the molecular mechanisms of TNBC metastasis is crucial for developing novel therapies. My postdoctoral work unveiled the involvement of a complex epithelial-mesenchymal transition (EMT) signaling in TNBC metastasis formation. Unexpectedly, I observed that TNBC metastases express mesenchymal markers including vimentin (Vim). While studying the role of Vim in TNBC metastasis, I identified a novel mechanism of metastatic colonization, where cancer cell clusters seed the lungs and then “declusterize” in a Vim-dependent manner into highly proliferative single cells, eventually forming clinically detectable metastases (unpublished). Understanding and addressing this novel process of cancer cell colonization is crucial, as it renders cancer cells undetectable by clinical radiologic imaging until the emergence of large metastases.

The objective of this project is to decipher the mechanisms driving this novel colonization process. It is divided into two independent yet complementary work packages: (1) Assess the impact of the microenvironment and chemotherapy on cancer cell declusterization, and (2) Elucidate the molecular mechanisms of TNBC metastatic colonization. By leveraging advanced culture models, cutting-edge imaging, and single-cell RNA sequencing, this project aims to provide valuable insights into TNBC metastasis potentially revealing therapeutic strategies that can prevent, limit, or halt metastatic spread, and therefore improve patient outcomes.