Journal Article


Shiaw-Yih Lin
Gordon B Mills
Bryan Hennessy
Christopher P Vellano
Jun Yin
Zhenlin Ju
Qinghua Yu
Yiling Lu
Hui Dai
Wei Mo
and 4 others


Medicine & Nursing

patient response ovarian cancer large scale tumor cells cancer cell lines gene expression profiles gene expression cancer patients

Improved prediction of PARP inhibitor response and identification of synergizing agents through use of a novel gene expression signature generation algorithm. (2016)

Abstract Despite rapid advancement in generation of large-scale microarray gene expression datasets, robust multigene expression signatures that are capable of guiding the use of specific therapies have not been routinely implemented into clinical care. We have developed an iterative resampling analysis to predict sensitivity algorithm to generate gene expression sensitivity profiles that predict patient responses to specific therapies. The resultant signatures have a robust capacity to accurately predict drug sensitivity as well as the identification of synergistic combinations. Here, we apply this approach to predict response to PARP inhibitors, and show it can greatly outperforms current clinical biomarkers, including BRCA1/2 mutation status, accurately identifying PARP inhibitor-sensitive cancer cell lines, primary patient-derived tumor cells, and patient-derived xenografts. These signatures were also capable of predicting patient response, as shown by applying a cisplatin sensitivity signature to ovarian cancer patients. We additionally demonstrate how these drug-sensitivity signatures can be applied to identify novel synergizing agents to improve drug efficacy. Tailoring therapeutic interventions to improve patient prognosis is of utmost importance, and our drug sensitivity prediction signatures may prove highly beneficial for patient management.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Shiaw-Yih Lin, Gordon B Mills, Bryan Hennessy, Christopher P Vellano, Jun Yin, Zhenlin Ju, Qinghua Yu, Yiling Lu, Hui Dai, Wei Mo and 4 others

Experts in our system

Gordon B Mills
Royal College of Surgeons in Ireland
Total Publications: 4
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33