Journal of Stem Cell Research & Therapy

Cancer stem cells (CSC), genetic drivers and therapeutic targeting via CCR5

11^th Annual Conference on Stem Cell and Regenerative Medicine

October 15-16, 2018 Helsinki, Finland

Richard G Pestell

Pennsylvania Cancer and Regenerative Medicine Center, USA

Keynote: J Stem Cell Res Ther

Abstract:

Statement of the Problem: Both Cancer Stem cell (CSCs) and normal tissue stem cells possess self-renewal capacity in CSCs self-renewal is deregulated. The term stemness is referred to the integrated functioning of molecular programs that govern and maintain the stem cell state. CSC possesses clinically relevant properties as they (1) contribute to metastasis (2) survive many commonly employed cancer therapeutics (3) Express transcriptional signatures that are predictive of poor patient survival. In order to target CSC it is necessary to define tractable molecular genetic drivers.

Findings: Specific genetic drivers of CSC were defined in mice including NFkB, cyclin D1, c-Jun, p21Cip1, Dach1 (retinal determination gene network), nuclear receptor acetylation sites and the G-protein coupled receptor CCR5. CCR5 was induced by a variety of mammary oncogenes and current chemotherapies. Small molecular inhibitors of CCR5 reduced cancer stem cells number. Enhanced cancer cell killing induced by standard chemotherapy and abrogated cancer metastasis in vivo. CCR5 inhibitors were effective independently of the genetic driver of the breast cancer.

Conclusion: Because CCR5 expression is induced in breast cancer cells, but not in normal epithelial cells and CCR5 inhibitors enhanced cell killing of standard therapies, a reduction in chemotherapy dose and thereby reduction in side effects is feasible. CCR5 inhibitors have been extensively studied and proven safe in humans for HIV therapy, therefore repurposing for selective CSC treatment of breast cancer metastasis appears feasible.

Biography :

Richard G Pestell is the President for the Pennsylvania Cancer and Regenerative Medicine Center, Pennsylvania. He is an expert in Oncology and Endocrinology. He worked as the Director of two NCI designated Cancer Centers and Executive Vice-President of Thomas Jefferson University. His research interest is in stem cells and cancer. His studies identified six distinct molecular genetic drivers of cancer stem cells in vivo and have developed technology to target cancer stem cells and thereby improve therapy responsiveness. His studies of cell fate determination factors have identified a unique genetic pathway that bridges activity of normal and cancerous stem cells.

E-mail: richard.pestell@gmail.com