A Gene Expression Profile of BRCAness that Predicts for Responsiveness to Platinum and PARP Inhibitors
Abstract
We have developed a 60-gene expression profile that may identify tumors with a BRCAness phenotype which is characterized by heightened sensitivity to chemotherapy (platinum and PARP inhibitors) and improved overall survival. We found that our profile can track diverse molecular mechanisms that cause defective homologous recombination (HR) in the absence of BRCA1 or BRCA2 mutations. Furthermore, we found that the BRCAness profile was associated with overall survival and response to platinum chemotherapy in vitro and in vivo using several metrics of clinical platinum sensitivity including disease free survival, achievement of complete response after first line therapy and percent progression free survival at 4 months, 6 and 18 months. Multivariate analysis and independent validation of the profile in patients from other institutions demonstrated that it maintained an independent association with disease free and overall survival. Our current studies are focusing on assessing the correlation of the profile with PARP inhibitor responsiveness, and evaluating the reproducibility of the profile using the DASL mRNA assay in formalin fixed, paraffin-embedded ovarian cancer specimens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2011
- Accession Number
- ADA553205
Entities
People
- Panagiotis A Konstantinopoulos
Organizations
- Beth Israel Deaconess Medical Center