학술논문
Homologous Recombination Deficiency: Concepts, Definitions, and Assays
Original Article
Original Article
Document Type
Report
Author
Stewart, Mark D.; Vega, Diana Merino; Arend, Rebecca C.; Baden, Jonathan F.; Barbash, Olena; Beaubier, Nike; Collins, Grace; French, Tim; Ghahramani, Negar; Hinson, Patsy; Jelinic, Petar; Marton, Matthew J.; McGregor, Kimberly; Parsons, Jerod; Ramamurthy, Lakshman; Sausen, Mark; Sokol, Ethan S.; Stenzinger, Albrecht; Stires, Hillary; Timms, Kirsten M.; Turco, Diana; Wang, Iris; Williams, J. Andrew; Wong-Ho, Elaine; Allen, Jeff
Source
The Oncologist. March 2022, Vol. 27 Issue 3, p167, 8 p.
Subject
Language
English
ISSN
1083-7159
Abstract
Implications for Practice Analyzing deficiencies in the homologous recombination repair (HRR) machinery becomes increasingly important to identify patients responding to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors. Ovarian, breast, pancreatic, and [...]
Background: Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting. Methods: Friends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status. Results: This publication provides findings from the group's discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community. Conclusion: Overall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors. Key words: homologous recombination; poly(ADP-ribose) polymerase inhibitors; BRCA1; BRCA2; biomarkers, tumor; DNA repair.
Background: Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting. Methods: Friends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status. Results: This publication provides findings from the group's discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community. Conclusion: Overall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors. Key words: homologous recombination; poly(ADP-ribose) polymerase inhibitors; BRCA1; BRCA2; biomarkers, tumor; DNA repair.