Dr. Michael Kinnaman, MMF Research Fellow, shares his research summary

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I am currently working in a lab that focuses on studying how cancer evolves, or changes and adapts over time, to a point where it spreads from the original site of disease to other organs in the body. My research specifically focuses on applying my lab's expertise to studying different types of pediatric sarcomas. I currently have two active projects studying cancer evolution in both osteosarcoma and rhabdomyosarcoma.

Osteosarcoma is the most common pediatric bone tumor and there have been no significant advances with regards to therapy or overall survival over the last three decades. There are approximately 400 new cases each year that arise in children and adolescents younger than 20 years of age. Unfortunately, only 20% of patients who present with or develop metastases will survive.

To help improve therapy and our understanding of osteosarcoma, my project's goal is to characterize the tumor cells that are resistant to our current therapy. These cells are the bad actors that we need to characterize in order to cure this disease. To do this we will be doing whole genome sequencing, which allows us to map out the entire genetic code of a cancer cell, on patients' tumor samples at different time points throughout treatment. We will then compare the genetic makeup of each sample to the samples collected from earlier in a patient's treatment to see how the tumor has changed. This will allow us to not only identify the resistant tumor cells but also characterize and describe their genetic makeup. We hope this new information will lead to new treatment and treatment strategies that are specifically targeted towards these resistant tumor cells, improving outcomes for our patients with osteosarcoma.

My other research project involves studying evolution in rhabdomyosarcoma (cancer that typically begins in muscle cells), which is the most common type of soft tissue sarcoma in children. Only about 70% of patients who are diagnosed with rhabdomyosarcoma will be cured, and outcomes for adolescent patients is significantly worse.

To help improve therapy and our understanding of rhabdomyosarcoma, we are studying tumor samples that were donated by two patients at MSKCC, who had unusually aggressive forms of this cancer and ultimately died from their disease. They both consented to have a research autopsy performed after they died, donating their tumor samples to the research community as their last wish. Similar to the osteosarcoma project, we will be using genomic sequencing on the samples that were acquired to explain why their cancers were so resistant to treatment. This sequencing information will allow us to construct a genetic timeline of how their tumors changed and evolved over time. We believe this information will be

critical in deepening our understanding of how to better treat this disease in the future and improve outcomes for future patients diagnosed with rhabdomyosarcoma. Future research directions in our lab will be directed at studying cancer evolution in translocation driven pediatric sarcomas such as Ewing's sarcoma and desmoplastic small round cell tumor.