Homologous recombination deficiency: Exploiting the fundamental vulnerability of ovarian cancer
By P. Konstantinopoulos, Raphael Ceccaldi, G. Shapiro, A. D’Andrea. Cancer Discovery, 2015
820 citations recorded by the source corpus.
Approximately 50% of epithelial ovarian cancers (EOCs) exhibit defective DNA repair via homologous recombination (HR) due to genetic and epigenetic alterations of HR pathway genes. Defective HR is an important therapeutic target in EOC as exemplified by the efficacy of platinum analogues in this disease, as well as the advent of poly-ADP ribose polymerase inhibitors which exhibit synthetic lethality when applied to HR deficient cells. Here, we describe the genotypic and phenotypic characteristics of HR deficient EOCs, discuss current and emerging approaches for targeting these tumors, and present challenges associated with these approaches focusing on development and overcoming resistance.
Subfields: Cell Biology, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/6f7abd5d3d05d24dc1517c7b47aa071419e0e604
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Citations in the corpus
- ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease†. (2019, methodology): “of HRD that has been incorporated into clinical practice, and this remains an active area of investigation.(39) Bowman et al(40) demonstrated that higher levels of oestrogen”
- A decade of clinical development of PARP inhibitors in perspective (2019, background): “Numerous mechanisms of acquired resistance to PARPi have been described in pre-clinical and clinical studies [65, 66]; these can be grouped into three main classes (Figure 2).”
- ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease (2019, background): “Overall, there is currently no prospectively validated biomarker of HRD that has been incorporated into clinical practice, and this remains an active area of investigation [39].”