Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer
Michal M Hoppe, Patrick Jaynes, Joanna D Wardyn, Sai Srinivas Upadhyayula, Tuan Zea Tan, Stefanus Lie, Diana GZ Lim, Brendan NK Pang, Sherlly Lim, Joe Yeong, Anthony Karnezis, Derek S Chiu, Samuel Leung, David G Huntsman, Anna S Sedukhina, Ko Sato, Monique D Topp, Clare L Scott, Hyungwon Choi, Naina R Patel Show all
EMBO MOLECULAR MEDICINE | WILEY | Published : 2021
Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A-priori identification of platinum resistance is therefore crucial to improve on standard first-line carboplatin-paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum-induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK-compliant study of pre-treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ. In a discovery cohort (n = 284), RAD51-High tumours had shorter progression-free and overall survival ..View full abstract
Awarded by Singapore Ministry of Health's National Medical Research Council Transition Award
Awarded by Singapore Ministry of Health's National Medical Research Council Individual Research Grant
Awarded by Singapore Ministry of Health's National Medical Research Council Clinician Scientist Award
We thank the patients from the cohorts described in this paper, who generously consent to their tissues being analysed for research. We also thank Prof. Ashok Venkitaraman and Prof. George K Chandy for their critical review of the manuscript. This work was supported by the Cancer Science Institute of Singapore, National University of Singapore PhD Graduate Scholarship to MMH, the Singapore Ministry of Health's National Medical Research Council Transition Award (NMRC/TA/0052/2016) to ADJ, the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative to ADJ, the Singapore Ministry of Health's National Medical Research Council Individual Research Grant (NMRC/CIRG/1400/2014) and Clinician Scientist Award (NMRC/CSA-INV/0016/2017) to DSPT, the CRUK Imperial Centre to NRP, the Imperial Experimental Medicine Centre (SCOTROC4 TMA construction) and the Cancer Research UK and Ovarian Cancer Action to RB.