Cancer Stem Cells

CSCs self-renewal, metastasis, chemoresistance

Breast cancer is the most frequently diagnosed malignancy in women and the major cause of patient death is due to invasiveness and dissemination of the tumor to distant secondary sites. TGFβ signaling plays a major role in mediating these tumorigenic events and work from our laboratory has contributed to unravelling the complex oncogenic role of TGFβ. We made inroads into understanding cancer stem cell (CSC) biology. CSCs utilize their self-renewal ability to regenerate tumors, drive metastasis and are responsible for drug resistance. Accordingly, these cells constitute a key target for new therapeutics. We study the molecular mechanisms by which TGFβ signaling pathways and downstream targets modulate the self-renewal and metastatic capacities of CSCs using knockout strategies and preclinical orthotopic transplantation models.

We found new roles for the cyclin-dependent kinase (CDK4) and the inflammatory protein Cox2 in regulating cancer stemness in triple negative breast cancer (TNBC), the deadliest subtype of breast cancer. Blocking either of these pathways led to significant decreases in CSC and chemotherapy resistant cell numbers. We are currently expanding this line of research, aiming at disabling the self-renewing capabilities of CSCs by developing new molecules that efficiently target the two pathways.