# The Evolution of Sarcoma Drug Sensitivity through Time and Space

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $318,066

## Abstract

PROJECT SUMMARY
Approximately 16,000 people are diagnosed with sarcoma each year in the US. Sarcomas are the third most
common cancer affecting children constituting about 15% of all diagnosed childhood tumors. Bone tumors are
the rarest of all, with less than 3,500 cases a year or 0.2% of all cancers. Despite aggressive treatment, overall
5-year survival rates are ~60% and around 30% for metastatic disease.
There is limited data on bone sarcoma drug sensitivity beyond first line chemotherapy. In parallel, there are major
gaps in our understanding of sarcomas molecular hallmarks and drivers, with limited sequencing data available
beyond the exome. Critically, very few sarcomas have had whole-genome sequencing, longitudinal profiling or
multi-region sequencing to understand their spatio- and temporal-genomic variability. This variability is thought
to be critical to understanding treatment response and failure, and there remains an urgent need to relate these
molecular features to quantitative aspects of drug sensitivity in most tumor types.
We have established a pipeline to develop personalized bone sarcoma organoids to screen hundreds of drugs
and determine a drug resistance and sensitivity profile for each tumor. We pair this with whole-genome
sequencing to identify mutational correlates of drug sensitivity. Here we will take advantage of this pipeline to
study how the molecular and pharmacologic behavior of bone sarcomas differs spatially within a single patient
(Aim 1) and how they vary during their transition from curable primary to lethal metastatic disease (Aim 2). This
study will allow us to define how bone sarcoma metastases diverge and respond to therapy and identify
actionable drug sensitivities as well as create a detailed portrait of how bone sarcomas evolve under therapeutic
selective pressure, linked to clinical outcomes.

## Key facts

- **NIH application ID:** 11010048
- **Project number:** 3R01CA244729-05S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Paul Christopher Boutros
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $318,066
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11010048

## Citation

> US National Institutes of Health, RePORTER application 11010048, The Evolution of Sarcoma Drug Sensitivity through Time and Space (3R01CA244729-05S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11010048. Licensed CC0.

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