# Indiana University Center for Pediatric Pharmacology and Precision Medicine

> **NIH NIH P50** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $676,502

## Abstract

The progress in the treatment of many childhood cancers is a story of amazing successes. Survival for many
childhood malignancies has improved logarithmically over the past three decades. However, despite these
remarkable advances, 30% of children with cancer develop relapsed disease, the majority of whom die of their
diseases. Furthermore, many chemotherapeutic agents are associated with significant side effects—which can
be debilitating and even life threatening in some cases. Advances in biomarker discovery, including genomics,
pharmacogenomics, transcriptomics, and proteomics, offer great hope to these patients in terms of improved
therapeutic precision, safety, and efficacy. We propose to combine informed candidate genomics with targeted
proteomics in our focused multifactorial approach in parallel with whole genome sequencing to translate and
optimize therapeutics in children. Our overall hypothesis is that combinations of carefully selected biomarkers
are associated with toxicity and overall response to pediatric cancer chemotherapy; and that using highly
predictive biomarkers to guide therapy for individual children will result in improved outcomes. The objective of
this center grant application is to identify the best combinations of biomarkers to predict response and toxicities
and to evaluate the therapeutic benefit of treating children with life-threatening cancers who are at high risk for
severe adverse drug effects. We propose two interdisciplinary and closely interlinked projects supported by our
Administrative Core. Project I will test the hypothesis that using a precision medicine approach (incorporating
focused NGS based tumor molecular characterization and targeted germline pharmacogenomics) in selecting
individualized therapeutic strategies to relapsed and refractory pediatric sarcomas is superior to using a
traditional approach. Project I will also evaluate therapeutic combinations for treatment of relapsed pediatric
sarcomas informed by focused tumor molecular analysis using our own patient-derived cell lines and
xenografts and will aim to discover novel targets to refine our precision medicine approach to improve
outcomes in this deadly group of pediatric diseases. Project II will utilize a novel panel of plasma protein
biomarkers prognostic of hematopoietic cell transplant (HCT) therapy-related sinusoidal obstruction syndrome
in children as the basis of a randomized trial evaluating defibrotide (a drug approved in Europe for treatment of
SOS) for prevention of this potentially fatal treatment-associated liver toxicity. This proposal will make a
significant positive impact by providing critical information for physicians to make informed decisions for safer
and more effective use of drugs in children. Furthermore, our application will ensure that both training and
research, in pediatric and developmental pharmacology, remains at the forefront of the development and use
of all medications in children. The direct outcome of t...

## Key facts

- **NIH application ID:** 9974297
- **Project number:** 5P50HD090215-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** JAMIE L RENBARGER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $676,502
- **Award type:** 5
- **Project period:** 2016-09-22 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974297

## Citation

> US National Institutes of Health, RePORTER application 9974297, Indiana University Center for Pediatric Pharmacology and Precision Medicine (5P50HD090215-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9974297. Licensed CC0.

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