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Scientists awarded NIH grant to study bone sarcomas

Post Date:August 31, 2020 8:00 AM

Alice Soragni, PhD, and Paul Boutros, PhD, of the UCLA Jonsson Comprehensive Cancer Center have received a five-year, $2.4 million award from the National Institutes of Health to study bone sarcomas at the molecular level, which is critical to understanding why treatment can either have a positive outcome or fail.

Bone sarcomas are rare tumors that are poorly characterized at the molecular and drug-resistance level, and clinical outcomes have not significantly improved over the past decade. Despite aggressive treatment, the overall five-year survival rate for the disease is 60%, and it drops to 30% if the cancer spreads to other parts of the body.

Dr. Paul Boutros
Dr. Paul Boutros

“Bone sarcomas are incredibly rare tumors overall; however, they are more commonly diagnosed in children and young adults,” said Soragni, an assistant professor of orthopedic surgery at the David Geffen School of Medicine at UCLA. “We still don’t have a complete understanding of how these tumors respond to therapy and how responses change as bone tumors evolve and metastasize to other organs. By developing tumor organoid models, we will investigate their drug sensitivity and resistance profiles. At the same time, we will uncover the molecular features of each bone tumor using whole genome sequencing.”

The collaborating labs of Soragni and Boutros established a pipeline to develop bone sarcoma organoids — tiny 3D tumor models grown in the lab using clinical samples — in order to screen hundreds of drugs, paired with whole genome sequencing, to identify mutational correlates of drug sensitivity.

The grant will take advantage of this pipeline and help determine how the molecular and pharmacologic behavior of bone sarcomas differs spatially within a single patient and how  sarcomas vary during the transition from a curable, primary disease to a lethal, metastatic disease.

“This study will allow us to define how bone sarcoma changes, metastases diverge and respond to therapy, and identify actionable drug sensitivities,” said Boutros, a professor of urology and human genetics who serves as associate director of cancer informatics at the UCLA Institute for Precision Health and director of cancer data science at the Jonsson Cancer Center. “This will create the first detailed portrait of how bone sarcomas evolve under therapeutic selective pressure, linked to clinical outcomes.”

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