Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer

Autor: Samuel Leung, Sai Srinivas Upadhyayula, Anna S. Sedukhina, Anthony N. Karnezis, Diana G Z Lim, Clare L. Scott, Stefanus Lie, Sherlly Lim, Derek S. Chiu, Joanna D. Wardyn, David S.P. Tan, Joe P S Yeong, Ko Sato, Michal Marek Hoppe, Monique Topp, Stan B. Kaye, Brendan Pang, Robert S. Brown, Tuan Zea Tan, Hyungwon Choi, Anand D. Jeyasekharan, Jason J. Pitt, David G. Huntsman, Naina Patel, Patrick Jaynes
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Medicine (General)
endocrine system diseases
medicine.medical_treatment
RAD51
QH426-470
Carcinoma
Ovarian Epithelial
Medical and Health Sciences
chemistry.chemical_compound
0302 clinical medicine
Ovarian Epithelial
News & Views
Cancer
Ovarian Neoplasms
Articles
Biological Sciences
female genital diseases and pregnancy complications
Ovarian Cancer
ovarian cancer
Local
Paclitaxel
5.1 Pharmaceuticals
Molecular Medicine
Female
Development of treatments and therapeutic interventions
multiplexed IHC
endocrine system
DNA repair
Article
03 medical and health sciences
Rare Diseases
R5-920
immune exclusion
medicine
Carcinoma
Genetics
Humans
Platinum
Biomarkers & Diagnostic Imaging
Chemotherapy
Radar
business.industry
medicine.disease
Carboplatin
enzymes and coenzymes (carbohydrates)
Neoplasm Recurrence
030104 developmental biology
chemistry
HRD
Cancer research
Rad51 Recombinase
Neoplasm Recurrence
Local
Ovarian cancer
business
030217 neurology & neurosurgery
Zdroj: EMBO Molecular Medicine
EMBO Molecular Medicine, Vol 13, Iss 5, Pp n/a-n/a (2021)
EMBO molecular medicine, vol 13, iss 5
ISSN: 1757-4684
1757-4676
Popis: 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 compared to RAD51‐Low cases in univariate and multivariate analyses. The association of RAD51 with relapse/survival was validated in a carboplatin monotherapy SCOTROC4 clinical trial cohort (n = 264) and was predominantly noted in HR‐proficient cancers (Myriad HRDscore
Quantitative immunohistochemistry (qIHC) reveals that high expression of the DNA repair protein RAD51 in epithelial ovarian cancer (EOC) is associated with early relapse after platinum chemotherapy, and also with decreased cytotoxic T‐cell infiltration into tumors.
Databáze: OpenAIRE
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