The homologous recombination repair defective (HRD) gene detection is a test to assess the dysfunctional status of the homologous recombination repair (HRR) pathway in tumor cells. It can predict HRD status and its extent in prostate tumors by detecting specific genomic alterations. Alfa Cytology is committed to providing a comprehensive one-stop HRD gene detection service for prostate cancer.
Homologous recombination repair (HRR) is the preferred repair method for DNA double strand breaks (DSBs). Homologous recombination deficiency (HRD) usually refers to the dysfunctional state of HRR at the cellular level, which can be caused by a number of factors such as germline or somatic mutations and epigenetic inactivation of HRR-related genes, and it is often found in a variety of malignant tumors, especially in ovarian, breast, pancreatic ductal, and prostate cancers, etc.
Fig.
1 Present-day landscape of FDA-approved diagnostic tools for PARPi treatments. (Stewart, M. D., et al.
2022)
HRR is the preferred repair method for double strand breaks (DSBs), HRD produces specific, quantifiable, and stable genomic alterations, which can be used to predict the status and extent of HRD in tumors by establishing a genomic profiling-based assessment system, which is of value in guiding the clinical use of PARP inhibitors and platinum-based drugs in tumors such as prostate cancer. Currently, it is becoming increasingly important to analyze defects in homologous recombination repair (HRR) mechanisms, and prostate cancer is at the forefront of this development, but other cancer types may follow.
To date, the U.S. FDA has approved several companion or supplemental diagnostics to facilitate the selection of prostate tumors for PARPi therapy based on HR status.
Table 1. Companion diagnostics approved for selection of PARPi in prostate cancer. (Stewart, M. D., et al. 2022)
Assay | Sample | Therapy type | Indication | Trial |
BRACAnalysis CDx | Blood | Olaparib | For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. | PROfound Study |
FoundationOne CDx | Tumor | Olaparib | PROfound Study | |
FoundationOne Liquid CDx | Plasma | Olaparib | PROfound Study |
Biomarkers such as HR status play a critical role in therapy decisions for prostate cancer. It is therefore of utmost importance to build consensus on how to define HRD and the methodology for assessing HR status to promote alignment and optimal use of this biomarker to identify patients who would benefit from PARPi therapy. Alfa Cytology has continuously built and improved our core technology platform with the aim of focusing on developing innovative HRD gene detection service for prostate cancer.
Sample Preparation
Obtain tumor tissue samples or blood samples. For tissue samples, ensure that the tumor cell content is sufficient (usually ≥30% tumor cell percentage is required) to ensure the accuracy of the test results.
Genomic DNA Extraction
Genomic DNA is extracted from tumor tissue or blood, and the acquired genomic DNA is then tested for quality to ensure its suitability for subsequent genetic testing and analysis.
HRR-Related Gene Mutation Detection
Embryonic and somatic mutations in BRCA1/2 and other key HRR genes are detected by high-throughput sequencing to assess the homologous recombination repair capacity of tumors.
HRD Status Assessment
By calculating the genomic instability score (GIS) and detecting HRR gene mutations, the HRD status of the tumor was comprehensively analyzed, and genetic variants such as BRCA1/2, GIS scores, and HRD status determination were provided in the report.
Alfa Cytology aims to provide customized one-stop development services to support your innovations and breakthroughs in the field of prostate cancer therapy. If you are interested in our services, please don't hesitate to contact us for further information and pricing details.
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