Genomic and Epigenomic ctDNA Profiling in Liquid Biopsies from Heavily Pretreated Patients with DNA Damage Response-Deficient Tumors.

ABSTRACT:

Purpose

The development of DNA damage response (DDR)-directed therapies is a major area of clinical investigation; however, to date, PARP inhibitors (PARPi) remain the only approved therapy in this space. Major challenges to DDR-targeted therapies in the post-PARPi therapy era are the context dependency of DDR alterations and the presence of preexisting resistance in this heavily pretreated population. Blood samples from patients with tumors harboring defects in DDR genes were used to evaluate the feasibility of a liquid biopsy platform to detect complex genomic events such as BRCA1/2 reversions, homologous recombination deficiency (HRD) signatures, pathogenic variant allele status, and differentially methylated regions for accurate quantitation of tumor fraction.

Experimental d

SUBMITTER: Silverman IM 

PROVIDER: S-EPMC12485378 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature