# Liquid biopsy approaches to inform osteosarcoma prognosis and tumor evolution

> **NIH NIH R37** · DANA-FARBER CANCER INST · 2024 · $384,644

## Abstract

PROJECT SUMMARY/ABSTRACT
Osteosarcoma is an aggressive malignancy of the bone that effects children and young adults. The current
treatment standard for osteosarcoma utilizes the same chemotherapy that has been used for 30 years and
outcomes have remained unchanged. Efforts to improve therapy for this disease with novel agents and treatment
intensification have been largely unsuccessful. One potential reason for this is the lack of reliable prognostic
biomarkers for this disease. As a result, most new candidate treatment approaches are tested in patients with
relapsed or metastatic disease, excluding patients with newly diagnosed localized disease who may be at high-
risk of treatment failure.
Despite intensive research efforts to understand the biology of osteosarcoma, most studies have been
underpowered to correlate recurrent genomic features at diagnosis with clinical outcomes. Patterns of tumor
evolution that give rise to relapse have remained unstudied. Serial tumor biopsy samples for research are
unavailable for evolutionary studies due to the safety concerns associated with anesthesia and surgery in
children. Therefore, little is known about the genomic features of osteosarcoma that give rise to relapse.
Newly available liquid biopsy technologies enable the detection of circulating tumor DNA (ctDNA) in the blood of
patients with cancer. In some malignancies, ctDNA levels correlate with prognosis and changes in ctDNA levels
correspond to disease response and progression. In this project, a large collection of blood samples from patients
with osteosarcoma will be used to study the correlation between ctDNA levels and outcomes in newly diagnosed
localized osteosarcoma and validate ctDNA as a new prognostic biomarker.
Circulating tumor cells (CTCs) can also be isolated from the peripheral blood of patients with osteosarcoma and
provides an alternative source of tumor cells for profiling when tumor samples are not available. In this study,
CTCs from patients with osteosarcoma will be captured for single-cell profiling of tumor cells. Together with deep
sequencing of ctDNA, serial samples will be used to identify recurrent patterns of tumor heterogeneity and
disease evolution in osteosarcoma. These studies will fundamentally broaden the understanding of the
osteosarcoma genome, the natural history of the disease, and validate novel biomarkers of outcome that could
alter the way we treat patients with osteosarcoma in the near future.

## Key facts

- **NIH application ID:** 10883604
- **Project number:** 5R37CA244355-05
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Brian Crompton
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $384,644
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883604

## Citation

> US National Institutes of Health, RePORTER application 10883604, Liquid biopsy approaches to inform osteosarcoma prognosis and tumor evolution (5R37CA244355-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10883604. Licensed CC0.

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