March 3, 2016 | by Letisia Marquez
City of Hope researchers are working to uncover how cancer stem cells grow, and what can be done to stop them from multiplying. To figure that out, they study how certain proteins interact with a cell’s genetic material — and how that affects the complex processes that make cancer cells divide.
Yanhong Shi, Ph.D., professor and director in the Division of Stem Cell Biology Research, recently published a paper in the journal Nature Communications about a promising therapeutic target for glioblastoma, the most common and aggressive primary brain tumor.
Here, she answers questions about her research.
What’s the main finding of this study?
Targeting cancer stem cells includes either stopping their growth or killing them. This study identified the relationship between two proteins — TLX and TET3 — as a way to target glioblastoma stem cells (GSCs), which are critical for tumor formation, maintenance, metastasis and resistance to therapy. In this study, we showed that suppressing TLX expression or overexpression of TET3 will inhibit glioblastoma tumor progression and enhance patient survival. Additionally, in this study we developed an efficient system for delivering gene therapy into these cancer stem cells using dendrimer nanoparticles. These nanoparticles are able to deliver small interfering RNAs (siRNAs) into tumor stem cells efficiently to suppress TLX and, consequently, tumor formation.
What impact do you expect from the findings?
The clinical significance of this finding is that knocking out TLX in glioblastoma stem cells suppresses their tumor formation potential in vivo. Glioblastoma is a highly aggressive brain tumor; life expectancy is a little over a year after diagnosis, and patient survival is increased only marginally by current therapies. Our siRNA approach to suppress TLX in GSCs has great potential to improve outcomes and survival rates of glioblastoma patients.
Does publication of this research hold personal significance?
It is an acknowledgment of our continuous efforts to identify more effective therapeutic strategies for cancers, in particular, the deadly glioblastoma. Our team comprises stem cell biologists, cancer researchers and clinicians, nanotechnologists, bioinformaticians and graduate students all working toward a common goal: targeting cancer stem cells to suppress tumor formation and enhance patient survival.
Other study authors include Qi Cui, Su Yang, Peng Ye, E Tian, Guoqiang Sun, Jiehua Zhou, Guihua Sun, Xiaoxuan Liu, Chao Chen, Kiyohito Murai, Chunnian Zhao, Krist Azizian, Lu Yang, Charles Warden, Xiwei Wu, Massimo D’Apuzzo, Christine Brown, Behnam Badie, Ling Peng, Arthur Riggs and John Rossi.
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