Genomic, Transcriptomic, and Functional Alterations in DNA Damage Response Pathways as Putative Biomarkers of Chemotherapy Response in Ovarian Cancer.

Defective DNA damage response (DDR) pathways are enabling characteristics of cancers that not only can be exploited to specifically target cancer cells but also can predict chemotherapy response. Defective Homologous Recombination Repair (HRR) function, e.g.

Integration of computer-aided automated analysis algorithms in the development and validation of immunohistochemistry biomarkers in ovarian cancer.

In an era when immunohistochemistry (IHC) is increasingly depended on for histological subtyping, and IHC-determined biomarker informing rapid treatment choices is on the horizon; reproducible, quantifiable techniques are required. This study aimed to compare automated IHC scoring to quantify 6 DNA damage response protein markers using a tissue microarray of 66 ovarian cancer samples. Accuracy of quantification was compared between manual H-score and computer-aided quantification using Aperio ImageScope with and without a tissue classification algorithm.

Evaluating the potential of kinase inhibitors to suppress DNA repair and sensitise ovarian cancer cells to PARP inhibitors.

PARP inhibitors (PARPi) represent a major advance in the treatment of ovarian cancer associated with defects in homologous recombination DNA repair (HRR), primarily due to mutations in BRCA genes. Imatinib and PI3K inhibitors are reported to downregulate HRR and, in some cases, sensitise cells to PARPi. We investigated the ability of imatinib, and the PI3K inhibitors: NVP-BEZ235 and VS-5584, to downregulate HRR and sensitise paired ovarian cancer cells with mutant and reconstituted BRCA1 to the PARPi, olaparib and rucaparib.

Characterization and drug sensitivity of a novel human ovarian clear cell carcinoma cell line genomically and phenotypically similar to the original tumor.

NUCOLL43 is a novel ovarian clear cell carcinoma (O-CCC) cell line that arose from a primary culture of a patient's malignant ascites. The cells grow reliably in cell culture with a doubling time of approx. 45 hours and form colonies at high efficiency.