Glioblastomas (GBM) are highly recurrent and aggressive tumors that are associated with poor prognosis. Existence of glioma stem cells (GSCs) populations has been identified in these tumor that are associated with aggressive nature and recurrence of these tumors. These GSCs possess properties of stem cells that includes self-renewable, proliferation and therapeutic resistance contributing to the poor clinical outcome. Thus targeting these stem cells in tumors offers a reliable and potential target to improve treatment outcome in glioblastoma. Our laboratory focuses on understanding the role of autophagy in the existence of cancer stem cells (CSCs) in tumors, specifically in high grade gliomas. We have identified the role of autophagy in the maintenance of GSCs as well as Temozolomide (TMZ)-induced therapeutic response, the most commonly used treatment against GBM. Using primary as well established cell lines of human origin, we have demonstrated role of autophagy in maintenance of glioma stem cell population. Further, our experimental data suggested that autophagy provides survival advantage to glioblastoma cells in response to chemotherapy. More interestingly, we have identified that TMZ treatment significantly increases the population of GSCs that is associated with upregulation of autophagy.  Our findings implicate that, inhibition of autophagy prevented TMZ-induced increased GSC population, suggesting a critical role for autophagy in therapy-induced generation of GSC pool. Currently, we are generating some exciting data that suggest important role of autophagy in GSC and use of various autophagy modulators as combinational agents to overcome chemoresistance in these GSC. CSC is relatively unexplored field with high potential and present study is providing some important data that may form basis for defining the mode of therapy in future.

Keywords: Cancer stem cells, Glioblastoma, Autophagy, Chemotherapeutics

Meenakshi Tiwari did post-graduation in Biochemistry from Jiwaji University and was awarded Gold Medal for securing first position in merit. She also received prestigious NET/LS/CSIR JRF and ICMR fellowship for pursuing Ph.D. After masters, Dr. Tiwari joined Ph.D. program at Sanjay Gandhi Post Graduate Institute of Medical Sciences, India, as CSIR JRF.  During her Ph.D. she studied molecular mechanism of chemotherapeutic agents in glioblastoma cells and was awarded Gold Medal for best paper and excellence in research. Later, she joined as Postdoctoral fellow at UTHSCSA, San Antonio, Texas, USA (2007-2013). Currently she is working as Associate Professor in the department of Biochemistry at All India Institute of Medical Sciences-Patna. Dr. Tiwari is running various extramural funded projects funded by Government of India. Her research interest included role of apoptosis and autophagy in chemotherapeutics in cancer, neurodegeneration, stem cells/cancer stem cells, infertility and congenital anomalies.