- Research Program Mentor
PhD Doctor of Philosophy
Cancer Stem Cells/ RNA biology/ Adult and pediatric brain cancers
Understanding the molecular mechanisms of tumor recurrence using glioblastoma as a model
One of most important issues with treatment of Glioblastoma (GBM), one of the deadliest forms of brain tumor, is that after removal, it recurs within a short span and that too, very aggressively. Earlier findings have established that this is because of the residual Glioma-stem-like cell (GSC) population, that continues to grow and proliferate even after the removal of bulk tumor, thus, suggesting that alongwith the removal of GBM cells, it is important to target GSCs as well. Traditional anti-GBM drug discovery relies on the research performed in cancer cells growing in in vitro conditions, which is often supplemented with growth facilitating nutrients that tend to reduce stress. In contrast, a GBM cell growing in the brain of a patient encounters a very different microenvironment crowded with large number of other cells, both cancerous and non-cancerous, along with reduced nutrient and oxygen availability, and increased cell stress due to immune regulators. Therefore, not surprisingly, most of the proposed drugs based on the studies conducted in cell culture, come across as harsh chemicals that do not discriminate between normal and cancer cells; rather target all proliferating cells leading to severe adverse effects in patients. In their in vivo tumor microenvironment, GBM cell, including GSC, expends a lot of energy in responding to these microenvironmental stimuli and activate novel signalling pathways to survive. Thus, identification and effective targeting of these in vivo specific signalling regulators are key to effective treatment of GBM. Major focus of this study is to understand how microenvironment-driven changes in tumor cells enable them to survive and thrive in stressful in vivo conditions. The findings from the study could potentially give us better insights into the biology of GSCs and most likely explain the mechanism as to how these cells continue to thrive upon tumor removal and develop into a more aggressive one.