# Personalized cancer models to discover and develop new therapeutic targets.

> **NIH NIH U01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $470,312

## Abstract

PROJECT SUMMARY/ABSTRACT
The wealth of data on the genomics of cancer provides a great opportunity to develop more effective targeted
therapies. However, many commonly mutated cancer genes resist efforts to target with drugs, genetic
heterogeneity of tumors confounds choice or efficacy of drugs, and development of resistance to commonly
used therapies is common, leaving few alternatives. New approaches are needed to address these
challenges. Exploiting cellular vulnerabilities generated as a result of mutations in commonly mutated genes,
e.g. synthetic lethality, is a promising approach, as illustrated by the recent approval of the PARP inhibitor
olaparib in ovarian cancer. We have developed and optimized a synthetic lethal discovery platform that entails
high throughput screening to identify novel targets in patient-derived cancer cell cultures and isogenic cell
systems. Integration of functional screen results with both patient specific (N of 1) and population-based
genomic data is used to prioritize targets useful to the greatest number of patients and in the most appropriate
genomic and molecular contexts. Prioritized targets undergo exhaustive confirmation and orthogonal
validation in physiologically-relevant settings including genomically characterized patient-derived cell cultures,
organoids and patient derived xenograft (PDX) models. Synthetic lethal genes identified with our platform are
conserved across species, have been confirmed as candidate drug targets across multiple human cancer
types and have led to an investigator initiated clinical trial, illustrating the translational utility of our platform.
The outcome of this proposal will be novel validated targets and therapeutic strategies to several human
cancer types including those resistant to standard of care agents and a deeper understanding of the biology of
several major cancer genes.

## Key facts

- **NIH application ID:** 10228567
- **Project number:** 5U01CA217883-05
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** CHRISTOPHER J KEMP
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $470,312
- **Award type:** 5
- **Project period:** 2017-09-14 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228567

## Citation

> US National Institutes of Health, RePORTER application 10228567, Personalized cancer models to discover and develop new therapeutic targets. (5U01CA217883-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10228567. Licensed CC0.

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