Special Issue "Homolog Recombination Deficiency, Genetics in Ovarian Cancer"

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 2441

Special Issue Editor

Prof. Dr. Amit Manulal Oza
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Guest Editor
University Health Network University of Toronto, Toronto, Canada
Interests: ovarian cancer; BRCA1/2; homologous recombination; drug development; targeted therapy; disease monitoring; quality of life; equitable access

Special Issue Information

Dear Colleagues,

The seminal discovery of BReast CAncer genes 1 and 2 (BRCA1/2) nearly two decades ago catapulted scientific and clinical research activities forward and has resulted in multiple changes in the paradigm of care in cancer. Responsible for safeguarding DNA repair by way of tumor suppression and damaged DNA destruction, BRCA1 and 2 work in concert to provide the necessary coordination of cellular fidelity and if they go awry, then the risk of developing cancer increases. Breakdown of this process—known as Homologous Recombination Deficiency (HRD)—is a contributory factor in the etiology of breast and other solid tumors of the ovary, pancreas, and prostate. The delicate interplay between the underlying genetics and the vulnerabilities of BRCA1/2 and HRD has been successfully exploited in preclinical and clinical domains, heralding the clinical adoption of PARP inhibitors in several of these cancers, particularly ovarian cancer, with a notable impact on progression, overall survival, and quality of life.

Contemporary ovarian cancer management incorporates comprehensive approaches to BRCA1/2 and genomic testing to identify the potential for inherited risk (and hence prevention for family members) as well as prediction of therapeutic outcome, most notably with PARP inhibitors. Emerging research on resistance mechanisms will help to guide the potential for future precision therapy to overcome this, or at least avoid futile therapy. This Special Issue will go beyond examining the role of BRCA1/2 and HRD in ovarian cancer and delve into key areas of development in preclinical and clinical domains. Current research is being conducted to advance precise therapeutic approaches (surgical, radiation, and drug development), disease monitoring technologies, equitable access to testing, and therapeutic access to agents such as PARPi and to identify issues related to the impact of treatment chronicity on quality of life.

Prof. Dr. Amit Manulal Oza
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ovarian cancer
  • BRCA1/2
  • homologous recombination
  • drug development
  • targeted therapy
  • disease monitoring
  • quality of life
  • equitable access

Published Papers (2 papers)

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Research

Article
BRCA2 Promotes Spontaneous Homologous Recombination In Vivo
Cancers 2021, 13(15), 3663; https://doi.org/10.3390/cancers13153663 - 21 Jul 2021
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Abstract
Background: BRCA2 is known to be a tumor suppressor involved in homologous recombination repair and presumed to prevent genome instability in normal tissues prior to the development of tumors. Typical assessment of BRCA2 deficiency on the genome involves cell-based models using cancer cells [...] Read more.
Background: BRCA2 is known to be a tumor suppressor involved in homologous recombination repair and presumed to prevent genome instability in normal tissues prior to the development of tumors. Typical assessment of BRCA2 deficiency on the genome involves cell-based models using cancer cells with mixed genetic contexts, but the role in normal tissue in vivo has not been clearly demonstrated. Methods: Using conditional deletion of Brca2 exon 11, the region containing all eight BRC repeats, in the retinal pigment epithelium and the pink-eyed unstable mouse model, we evaluate the frequency of DNA deletion events. Results: In the current study, we show that conditional loss of Brca2 exon 11 results in a decreased frequency of spontaneous homologous recombination compared to wild-type mice. Of note, we observe no apparent concomitant increase in events that indicate single-strand annealing by the pink-eyed unstable mouse model. Conclusions: Therefore, our results demonstrate that BRCA2, as expected, is required for high-fidelity homologous recombination DNA repair in normal tissues, here in a tissue undergoing normal proliferation through normal development. Full article
(This article belongs to the Special Issue Homolog Recombination Deficiency, Genetics in Ovarian Cancer)
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Article
The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks
Cancers 2021, 13(12), 2994; https://doi.org/10.3390/cancers13122994 - 15 Jun 2021
Cited by 4 | Viewed by 1351
Abstract
PARP inhibitor (PARPi) sensitivity is related to tumor-specific defects in homologous recombination (HR). Therefore, there is great clinical interest in tests that can rapidly and reliably identify HR deficiency (HRD). Functional HRD tests determine the actual HR status by using the (dis)ability to [...] Read more.
PARP inhibitor (PARPi) sensitivity is related to tumor-specific defects in homologous recombination (HR). Therefore, there is great clinical interest in tests that can rapidly and reliably identify HR deficiency (HRD). Functional HRD tests determine the actual HR status by using the (dis)ability to accumulate RAD51 protein at sites of DNA damage as read-out. In this study, we further improved and calibrated a previously described RAD51-based functional HRD test on 74 diagnostic formalin-fixed paraffin-embedded (FFPE) specimens (RAD51-FFPE test) from endometrial cancer (EC n = 25) and epithelial ovarian cancer (OC n = 49) patients. We established optimal parameters with regard to RAD51 foci cut-off (≥2) and HRD threshold (15%) using matched endometrial and ovarian carcinoma specimens for which HR status had been established using a RAD51-based test that required ex vivo irradiation of fresh tissue (RECAP test). The RAD51-FFPE test detected BRCA deficient tumors with 90% sensitivity and RECAP-HRD tumors with 87% sensitivity, indicating that it is an attractive alternative to DNA-based tests with the potential to be applied in routine diagnostic pathology. Full article
(This article belongs to the Special Issue Homolog Recombination Deficiency, Genetics in Ovarian Cancer)
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