FUNDED INVESTIGATORS

Julio Aguirre-Ghiso, Ph.D. Eduardo Farias, Ph.D. Emily Bernstein, Ph.D.
Icahn School of Medicine at Mount Sinai    Icahn School of Medicine at Mount Sinai    Icahn School of Medicine at Mount Sinai

Activating a Dormancy Program in Disseminated Tumor Cells

Drs. Aguirre-Ghiso, Farias and Bernstein joined forces to pursue a long-standing effort of the Waxman Foundation—to investigate the underexplored area of cancer biology pioneered by Dr. Lilly Ossowski. They compare active and dormant cells through the use of squamous cell carcinoma models and the breast cancer models of MMTV-Neu in both in vivo and in vitro models. Their work led to the novel finding that high nuclear expression of the nuclear receptor NR2F1 is associated with the dormant phenotype and regulated by the low ERK/p38 profile characteristic of dormancy. They focus on opposing roles of retinoid receptors beta, alpha, and epsilon in regulating the dormant phenotype. This enables the use of pharmaceutical agents to manipulate dormancy in both models. They look at the tumor microenvironment and dormant sites in lung and bone marrow.

They have found that the dormant phenotype is associated with nuclear expression of NR2F1 and regulated by the low ERK/p38 profile. The focus on opposing roles of retinoid receptors in regulating the dormant phenotype has allowed the use of pharmacological agents to manipulate dormancy and use inhibitors and activators to explore the ability of critical pathways.