|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|
Studying Dormancy in Disseminated Tumor Cells
The long-term goal of the research conducted by Drs. Aguirre-Ghiso, Farias and Bernstein is to prevent metastasis by targeting the biology of dormant disseminated tumor cells.
Their SWCRF-funded project discovered in models of head and neck, breast and prostate cancer that restoration of vitamin A signaling could activate tumor cell dormancy. We identified the target genes that vitamin A regulates and how specific regulatory mechanisms of gene production is used to turn on mechanisms of dormancy.
They found that:
1) the dormancy program can be activated by host signals, that it is long-lived and detectable in dormant tumor cells in patients and that it overlaps with aging or senescence gene programs;
2) specific analogs of the vitamin A signaling in combination with epigenetic drugs (5-Aza-C) in the clinic “reprogram” tumor cells to enter stable dormancy, and
3) autophagy, an energy production mechanism that promotes cell survival, might be responsible for the induction of dormancy.
The collaborators hypothesize that understanding these mechanisms will allow the induction of residual cancer cell dormancy as well as eradicating dormant cancer cells via the activation of cell death. This approach used in the adjuvant setting may have significant impact in preventing relapse after first line therapies.