# Targeting vulnerabilities of therapy-resistant cancer cell states with small molecules

> **NIH NIH U01** · BROAD INSTITUTE, INC. · 2020 · $1,196,074

## Abstract

ABSTRACT
Targeted therapies and immunotherapies are two of the most transformative and promising advances in
cancer treatment over the last two decades. Yet they, like conventional chemotherapies, frequently succumb to
the ability of cancers eventually to resist therapeutic attacks on their vulnerabilities, reversing the initially
impressive clinical responses to these treatments. This project focuses on conserved non-mutational
mechanisms of resistance that are frequently encountered in resistance arising in multiple therapeutic
regimens across multiple cancer types. In the current phase of the CTD2 Network, we developed powerful new
tools and capabilities that enable the community to identify novel cancer vulnerabilities. The method relies on
the Cancer Therapeutics Response Portal (CTRP), which houses a large dataset of quantitative compound
sensitivity data and has been made available without restriction. Using CTRP, we found evidence for the
existence of at least one such common therapy-resistant state, associated with mesenchymal characteristics of
cancer cells. Importantly, this state emerges from treatment with either chemotherapy or targeted therapeutics
across several cancer types. This project aims to fully dissect this pathway, and to discover other such
pathways, to understand the bases of resistant-state vulnerabilities, and to learn how to exploit them
therapeutically in a safe and effective way.

## Key facts

- **NIH application ID:** 9987570
- **Project number:** 5U01CA217848-04
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** STUART L SCHREIBER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,196,074
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987570

## Citation

> US National Institutes of Health, RePORTER application 9987570, Targeting vulnerabilities of therapy-resistant cancer cell states with small molecules (5U01CA217848-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987570. Licensed CC0.

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