First of all, I am honored to be a research fellow of the Marguax Miracle Foundation for 2011.
My passion for research in oncology began during my medical training in India. When I was a resident at Miami Children’s Hospital I worked closely with a pediatric oncology team, which strengthened my desire to advance the horizons of therapeutic strategies in children with cancer. It did not take too long before I decided to come to Memorial Sloan-Kettering Cancer Center to pursue my fellowship. During my clinical year at MSKCC I noticed that sarcomas pose a major therapeutic challenge and we have yet to make significant progress in this field. I chose to work on Ewing sarcoma in the laboratory of Dr. Malcolm Moore at MSKCC, a pioneer in cancer research and a great mentor. His lab has been at the forefront in identifying cancer stem cells in many tumors and developing therapeutic strategies to target them. I am utilizing the resources available in clinic and lab to improve survival in children with Ewing sarcoma.
Ewing sarcoma is a rare cancer that occurs mainly in children and young adults. It can occur in bone or soft tissue and has high propensity for metastasis – especially to lung, bone and bone marrow. Despite developments in chemotherapeutic regimens, the outcome for metastatic Ewing sarcoma remains poor. It is characterized by specific chromosome translocations and up to 85% of the cases have the t(11;22)(q24;q12) translocation, resulting in a fusion gene between EWS (the EWS gene is on chromosome 22) and FLI1 (Fli-1, a protein that in humans is encoded by the human FLI1 gene aberrant expression is also associated with chromosomal abnormalities in humans). Efforts to identify specific gene targets and understand the transcriptional dysregulation have been difficult due to the unknown nature of the cell of origin. We are trying to solve this puzzle in the laboratory by transforming benign mesenchymal progenitor cells into sarcomas to see if we can ascertain exactly what changes are necessary for a normal stem cell to become malignant.
We are planning to introduce “second hits” to inactivate cell death pathways activated in response to DNA damage (siRNAl to p53, RB, BCL2), and to inactivate other potential tumor suppressor genes. We are studying the expression of various surface markers and genes that are over-expressed in Ewing sarcoma during transformation. We are also exploring tumor-stroma interactions in Ewing sarcoma to discover novel targets. We hope that our research will lead to identification of new drugs that will specifically aim at cancer stem cells and improve outcomes in Ewing sarcoma.
We thank you for supporting our research efforts at Memorial Sloan-Kettering Cancer Center.