# Towards rational design of combination therapeutic targets

> **NIH NIH U01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $446,027

## Abstract

Project Summary
Given the prevalence of crosstalk among oncogenic pathways and disease
heterogeneity, it has become increasingly apparent that combination therapies are
required to achieve long-term cure and to minimize development of resistance mutations
and escape pathways. The majority of existing combination therapies are developed in
an ad hoc fashion, namely one agent at a time, without systematic consideration of
potential complex interactions among the gene targets by leveraging disease-specific
omics data. Moreover, the existing combination therapies are based on targets of
existing drugs, which only represent a small portion of the human proteome. To this end,
we hypothesize that systematic identification of synergistic key regulators represents a
promising approach for nominating targets of combination therapy. Towards this goal,
we will forward engineer a platform for identifying synergistic regulatory nodes in a
cancer gene regulatory network as the targets for combination therapy. We will generate
disease-specific multi-omics data to construct an integrative gene regulatory network, a
pre-requisite for understanding the deregulated gene network in the cancer cells and for
developing effective and lasting therapy. We will focus our study on Philadelphia-like
acute lymphoblastic leukemia as a proof-of-principle. Our team proposes a novel
approach to this problem by leveraging the unique strengths of the investigators in
systems biology, genomics, proteomics, and translational research, as well as the large
cohort of patient samples available at our institutions. If successful, the proposed
framework would be a tremendous advance and paradigm shift to understand genetic
interactions among oncogenic pathways for eventual therapeutic intervention.

## Key facts

- **NIH application ID:** 10852887
- **Project number:** 5U01CA243072-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** SARAH KATHLEEN TASIAN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $446,027
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852887

## Citation

> US National Institutes of Health, RePORTER application 10852887, Towards rational design of combination therapeutic targets (5U01CA243072-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10852887. Licensed CC0.

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