Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model.
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 BRCA2, 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.
Authors
Polten Polten, Kutle Kutle, Stalp Stalp, Hachenberg Hachenberg, John-Neek John-Neek, Seyda Seyda, Ramachandran Ramachandran, Schmidtke Schmidtke, Obrizan Obrizan, Kokemüller Kokemüller, Steinemann Steinemann, Lühmann Lühmann, Behrens Behrens, Göhring Göhring, Bartels Bartels, Gronewold Gronewold, Neubert Neubert, Kamp Kamp, Schaudien Schaudien, Geffers Geffers, Hillemanns Hillemanns, Dörk Dörk, Klapdor Klapdor, Morgan Morgan, Schambach Schambach
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