# Systematic pharmacological targeting of the core mechanisms responsible for maintaining cancer cell state

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $473,035

## Abstract

PROJECT SUMMARY (30 LINES)
Tumors are strongly dependent on the aberrant activity of the tumor checkpoint modules that are responsible
for maintaining tumor cell-state or for inducing drug resistance. Thus inference of compounds and
combinations that can collapse the activity of such tumor checkpoints in vivo is extremely relevant toward
developing novel cancer therapeutics and rescuing drugs that induce relapse. The overall goal of this project is
explore the hypothesis that compounds or combinations that are computationally inferred to induce checkpoint
collapse (in vitro or in vivo) will translate to preclinical models, in terms of inducing tumor regression or
sensitivity rescue in vivo. Specifically, the project will aim at developing and experimentally validating novel
algorithms to: (1) Elucidate compound specific targets and effectors. This will be done under aim 1 by
extending the current VIPER and DeMAND algorithms as well as by developing additional structure- and
network-based algorithms to identify specific pathways and proteins whose activity is dysregulated by
compound activity. (2) Study synergistic compound activity from RNASeq profiles of individual compound
perturbations. This will be done under aim 2 by specifically studying and targeting the distinct mechanisms that
underlie synergistic drug activity. Developed algorithms will be used to prioritize combination therapy to treat
PDX models from the N of 1 pilot study. Finally developing a predictive framework for the assessment of
compound and compound combination toxicity. This will be done under aim 3 by integrating results from the
analysis of gene expression profiles following in vivo perturbations with established toxic compounds both from
publicly available databases and novel assays.

## Key facts

- **NIH application ID:** 9976488
- **Project number:** 5U54CA209997-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** ANDREA CALIFANO
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,035
- **Award type:** 5
- **Project period:** — → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976488

## Citation

> US National Institutes of Health, RePORTER application 9976488, Systematic pharmacological targeting of the core mechanisms responsible for maintaining cancer cell state (5U54CA209997-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976488. Licensed CC0.

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