Maria S. Sosa, Ph.D.

Our research program is dedicated to tackling one of the most formidable challenges in oncology: the prevention of cancer metastasis, which remains the leading cause of cancer-related deaths. We focus on the biology of dormant disseminated cancer cells (DCCs)—cells that can persist in a patient’s body for years after treatment of the primary tumor, only to later reactivate and form incurable metastases. By investigating both the intrinsic properties of DCCs and the microenvironmental factors that govern their dormancy and reactivation, our lab aims to uncover the mechanisms that underlie minimal residual disease and metastatic relapse.

A central theme of our work is understanding how transcriptional and pluripotency programs regulate DCC fate. We are particularly interested in the role of NR2F1, an orphan nuclear receptor we identified as a master regulator of dormancy in advanced tumors and as a prognostic marker in breast cancer. Our translational research seeks to exploit vulnerabilities in DCCs, with the goal of either inducing stable dormancy or eliminating these cells before they can seed new metastases. Notably, our discoveries have led to the development of novel dormancy-inducing therapies, including a new NR2F1 agonist, and the initiation of a clinical trial targeting metastatic prostate cancer by using all trans retinoic acid and azacytidine.

Our group also  investigates the mechanism of early dissemination of cancer cells from premalignant lesions, revealing new sources of DCCs and highlighting NR2F1’s function as a barrier to early dissemination. Through these efforts, we strive to advance the understanding of metastatic progression and develop innovative strategies to prevent cancer relapse.

Contributions to Science

1. Linde N, Casanova-Acebes M*, Sosa MS*, Mortha A, Rahman A, Farias EF, Harper K,TardioE,ReyesTorresI,JonesJ,CondeelisJ,MeradM,and Aguirre-GhisoJA. ”Macrophages orchestrate breast cancer early dissemination and metastasis”.Nat Communications.2018.doi: 10.1038/s41467-017-02481-5.
2. Borgen E*, Rypdal MC*, Sosa MS*, Renolen A, Schlichting E, Lønning PE, Synnestvedt M, NR2F1 stratifies dormant disseminated tumor cells in breast cancer patients”.Breast Cancer Res.2018 Oct 16;20(1):120. doi: 10.1186/s13058-018-1049-0.
3. Khalil B, Sanchez R, Rhaman T, Moritsch S, Rodriguez Martinez A, Farias E, Cheung JF,Nobre AR, Kale N, Sosa MS and Aguirre-Ghiso JA. " An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy". J. Exp. Med., 2022. doi: 10.1084/jem.20210836. co-corresponding authors.
4. *Rodriguez-Tirado C, *Kale N, Carlini MJ, Shrivastava N, Alcina Rodrigues, Khalil B, Bravo-Cordero JJ, Yan Hong, Alexander M, Ji J, Fariba Behbod, and Sosa MS. “NR2F1 is a barrier to dissemination of early stage breast cancer cells” Cancer Research, 2022.DOI:10.1158/0008-5472.CAN-21-4145.
5. Jose Javier Bravo-Cordero, Thomas U. Marron, Sosa MS, Juan Arriaga, Andrew L., Poulikos I. Poulikakos. “Frontiers of Medical Research: Cancer Turning remission into cures: Novel therapies to outpace drug resistance and metastasis.” Frontiers of Medical Research: Cancer, Science, 2023.
6. Singh DK, Farias E, Carcamo S, Hasson D, Sun D, Cheung J, Nobre AR, Kale K, Sosa MS,Bernstein E, and Aguirre-Ghiso JA. "5-Azacytidine-and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling "Cell Reports,2023.doi: 10.3390/cancers11050726. DOI 10.1007/s10585-023-10248-0
7. Daniela Michelatti, Sven Beye, Chiara Bernardi, Maria Luce Negri, Leonardo Morelli, Naiara Garcia Bediaga, Vittoria Poli1, Luca Fagnocchi, Sara Lago, Sarah D’Annunzio, Nicole Cona, Matteo Gianesello, Alice Turdo, Caterina D’ Accardo, Miriam Gaggianesi, Martina Dori, Mattia Forcato, Giuliano Crispatzu, Alvaro Rada-Iglesias, Maria Soledad Sosa, HT Marc Timmer, Silvio Bicciato, Matilde Todaro, Luca Tiberi and Alessio Zippo. “Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting a transcriptional memory”. Nature Communications, 2024. doi: 10.1038/s41467-024-46524-0.