# Combined Methylation and Mutation to Predict Response to PARP Inhibitors

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $596,715

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of the current proposal is to develop a clinically useful predictor of PARP inhibitor (PARPi)
sensitivity/resistance to spare toxicities and cost for patients unlikely to derive benefit. Our hypothesis is that a
combined mutation and methylation analysis performed immediately before initiation of therapy will provide a
useful predictor of PARPi response. To test this hypothesis, our approach is to complete development of a
high throughput and quantitative methylation assay for key HR genes and refine our assays using banked
tumor tissues formalin fixed paraffin embedded (FFPE) neoplastic samples from phase II PARPi trials, then
test these assays using samples from 4 large phase III randomized controlled trials (RCT) in OC and BC that
employ three different PARPi. We propose three specific aims:
 Aim 1: Develop a clinical grade, quantitative methylation assay and a combined methylation and
 mutation assay (MMA) to define those BRCA wildtype cancers with best response to PARP inhibitors.
 Aim 2: Validate the combined HRR mutation and methylation assay (MMA) as a predictor of PARPi
response in 2 randomized controlled trials of recurrent breast and ovarian cancer.
Aim 3: Validate MMA as a predictor of PARPi response in 2 randomized controlled trials for primary
treatment of advanced ovarian cancer.
Together, these studies will provide insight into mechanisms of PARPi sensitivity while developing a clinical
predictor for both breast and ovarian cancer, which could apply to other cancer types. These studies will lead
to more precise therapeutic application of PARP inhibitors, reducing toxicity and cost while maximizing patient
benefit.

## Key facts

- **NIH application ID:** 10378133
- **Project number:** 5R01CA237600-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** ELIZABETH MARY SWISHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $596,715
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378133

## Citation

> US National Institutes of Health, RePORTER application 10378133, Combined Methylation and Mutation to Predict Response to PARP Inhibitors (5R01CA237600-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10378133. Licensed CC0.

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