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Updated: Dec 29, 2025
Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
Published on: February 28, 2021
A profile on the FoundationFocus CDxBRCA tests
Lindsey Ford1, Juliet E Wolford1, Sandra M Brown2
1Chao Family Comprehensive Cancer Center, University of California Irvine Health, Orange, CA, USA.
Abstract:
Introduction: Poly(ADP-ribose) polymerase (PARP) inhibitors, including rucaparib, are the only targeted class of therapeutics approved for recurrent epithelial ovarian carcinoma with a predictive biomarker. Currently, three different PARP inhibitors are approved for either the treatment of ovarian cancer or maintenance of remission following chemotherapy. The Foundation Focus CDxBRCA is an FDA-cleared next-generation sequencing tumor tissue assay that detects somatic and sometimes germline mutations in BRCA1 and BRCA2 genes.Areas covered: The authors discuss the evolution of the ovarian cancer genomic testing landscape relative to PARP inhibition, with a focus on Foundation Focus CDxBRCA and CDxBRCA Loss of Heterozygosity (LOH), the complementary diagnostics (CDx) to rucaparib.Expert opinion: Relatively early in PARP inhibitor development, women with somatic and/or germline mutations in the BRCA1 and BRCA2 genes were found to have higher response rates to PARP inhibitors with longer durability than women who were BRCA wildtype. Other measures of homologous recombination deficiency including LOH have proven to be predictive biomarkers also. Because PARP biomarkers are genomic and complex, co-development of high-performance companion diagnostics was a high priority. The Foundation Focus test began as a next-generation sequencing assay capable of detecting germline (gBRCA) and somatic (sBRCA) mutations that predict response to rucaparib treatment. The addition of LOH to the assay was validated by a clinical trial supporting expansion of the Rucaparib FDA label to include maintenance of chemotherapy response.
Insights
Poly(ADP-ribose) polymerase (PARP) inhibitors and companion diagnostics like Foundation Focus CDxBRCA are crucial for treating ovarian cancer. Genomic testing identifies mutations predicting response to PARP inhibitors, improving patient outcomes.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- PARP inhibitors are approved for recurrent epithelial ovarian carcinoma, with rucaparib being a key example.
- Foundation Focus CDxBRCA is an FDA-cleared assay for detecting BRCA1/2 mutations, guiding PARP inhibitor therapy.
- Genomic biomarkers, including BRCA mutations and Loss of Heterozygosity (LOH), are vital for predicting response to PARP inhibitors.
Purpose of the Study:
- To discuss the evolution of genomic testing in ovarian cancer concerning PARP inhibition.
- To highlight the role of Foundation Focus CDxBRCA and CDxBRCA LOH as complementary diagnostics for rucaparib.
- To review the predictive value of BRCA mutations and LOH for PARP inhibitor efficacy.
Main Methods:
- Review of the literature on PARP inhibitors and ovarian cancer genomic testing.
- Focus on the Foundation Focus CDxBRCA assay and its validation for detecting germline and somatic BRCA mutations.
- Analysis of clinical trial data supporting the use of LOH as a biomarker and its inclusion in diagnostic assays.
Main Results:
- Women with BRCA1/2 mutations show higher response rates and durability to PARP inhibitors.
- Loss of Heterozygosity (LOH) is also a validated predictive biomarker for PARP inhibitor response.
- The Foundation Focus CDxBRCA assay, including LOH detection, supports rucaparib's expanded FDA label for maintenance therapy.
Conclusions:
- Genomic biomarkers and companion diagnostics are essential for targeted PARP inhibitor therapy in ovarian cancer.
- The co-development of high-performance diagnostics is critical due to the complexity of PARP biomarkers.
- Advancements in testing, like the inclusion of LOH, enhance the utility of PARP inhibitors and expand treatment options.
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