Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model
Abstract
Abstract Genetic profiling of a new HPV-negative cervical cancer model identified pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, and DNA damage repair pathways, including homologous recombination, non-homologous end-joining, and mismatch repair. Deficiencies in BRCA 2, RAD51 and MLH1 were among these actionable targets. The newly described cervical cancer model revealed sensitivity towards the PARP inhibitor olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. In contrast, BRCA1/2 -proficient cervical cancer cells exhibited greater resistance to these strategies. This study highlights the potential of in-depth genetic analysis to identify genetic susceptibilities to guide personalized medicine approaches.
Article Details
Authors (25)
Robert Polten
Ivana Kutle
Jan Lennart Stalp
Jens Hachenberg
Philipp John-Neek
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
Ann-Kathrin Seyda
Dhanya Ramachandran
Rafaela Schmidtke
Valeriia Obrizan
Lara Kokemüller
Doris Steinemann
Jonathan Lühmann
Yvonne Lisa Behrens
Gudrun Göhring
Stephan Bartels
Malte Gronewold
Lavinia Neubert
Jan C. Kamp
Dirk Schaudien
Robert Geffers
Peter Hillemanns
Thilo Dörk
Rüdiger Klapdor
Michael Morgan
Axel Schambach
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany