# Developing a Suite of Targeted Anticancer Drugs

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2023 · $515,200

## Abstract

Abstract
The stunning clinical success of Gleevec (imatinib) two decades ago appeared to usher in a new era for
cancer treatment, whereby a molecular defect in a patient’s tumor was known and could be exploited with
a selective drug. A suite of such selective drugs were envisioned, 100s of different drugs that could be
prescribed to appropriate patients based on tumor profiling of 100s of different potential defects.
Unfortunately this vision has not come to pass, and, with only a handful of approved drug-target pairs, the
full potential of personalized medicine in oncology has not been realized. While drugs such as imatinib (and
vemurafenib, osimertinib, and a few others) have been game-changers for those cancer subtypes (e.g.,
certain cancer types with Bcr-Abl translocation, BRAFV600E mutation, and EGFRT790M mutation, respectively),
there remain 100s of cancer subtypes and hundreds of exploitable molecular defects that are not matched
with drugs. The plodding progress of traditional drug discovery in this realm suggests new approaches are
needed to fully realize the potential of targeted therapy for oncology. My lab has developed a discovery
platform – from compound synthesis, to cell culture, to target identification, to sophisticated animal models,
to translation – that has resulted in 4 novel cancer drugs licensed and moving to cancer patients in 15 years.
Building off the observation that truly selective drugs that are successful in human cancer patients also show
exquisite selectivity in cell culture, we have identified compounds that have wide activity differential for killing
sensitive cell lines versus non-sensitive cell lines; through this method we have identified compounds with
>100-fold selectivity and that have advanced (or are advancing) to human cancer patients. In work for the
OIA we will create an unprecedented collection of complex-and-diverse compounds, with the novel twist
that these compounds will be biased for anticancer activity through incorporation of an electrophile.
Compounds able to induce selective death in a panel of >100 cancer cell lines and normal cell types will be
advanced through medicinal chemistry optimization. Top compounds will then progress through two parallel
tracks, 1) discovery of the biological target (basis for the anticancer selectivity), with our experience showing
that in most cases this work will reveal novel exploitable defects in cancer, and 2) translational advancement
through the pharmacokinetic/toxicology/efficacy studies and assessment of the ability to engage the immune
system, experiments needed to move the very best compounds to clinical trials in cancer patients. We have
demonstrated the ability to accomplish all parts of this workflow at a high level, enlisting key collaborators
as needed. Through this OIA we will increase our output 2-5-fold, meaning the discovery and development
of 4-10 novel cancer drug/target pairs during the 7 year OIA. As importantly, this work will provide a b...

## Key facts

- **NIH application ID:** 10734624
- **Project number:** 1R35CA283859-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Paul Hergenrother
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $515,200
- **Award type:** 1
- **Project period:** 2023-09-20 → 2030-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734624

## Citation

> US National Institutes of Health, RePORTER application 10734624, Developing a Suite of Targeted Anticancer Drugs (1R35CA283859-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10734624. Licensed CC0.

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