A5016366998- Epigenetics and DNA Methylation
- RNA modifications and cancer
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- MicroRNA in disease regulation
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- BRCA gene mutations in cancer
- Ovarian cancer diagnosis and treatment
- Microtubule and mitosis dynamics
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- Cancer-related Molecular Pathways
National Center for Advancing Translational Sciences
2022-2024
National Institutes of Health
2022-2023
Abstract PARP inhibitor (PARPi)–resistant BRCA-mutant (BRCAm) high-grade serous ovarian cancer (HGSOC) represents a new clinical challenge with unmet therapeutic needs. Here, we performed quantitative high-throughput drug combination screen that identified the of an ATR (ATRi) and AKT (AKTi) as effective treatment strategy for both PARPi-sensitive PARPi-resistant BRCAm HGSOC. The ATRi AKTi induced DNA damage R loop–mediated replication stress (RS). Mechanistically, kinase domain AKT1...
Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene ( BRCA )–mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway as cytotoxic further validated activity of CHK1 inhibitor (CHK1i)...
<div>Abstract<p>PARP inhibitor (PARPi)–resistant <i>BRCA</i>-mutant (BRCAm) high-grade serous ovarian cancer (HGSOC) represents a new clinical challenge with unmet therapeutic needs. Here, we performed quantitative high-throughput drug combination screen that identified the of an ATR (ATRi) and AKT (AKTi) as effective treatment strategy for both PARPi-sensitive PARPi-resistant BRCAm HGSOC. The ATRi AKTi induced DNA damage R loop–mediated replication stress (RS)....
<div>Abstract<p>PARP inhibitor (PARPi)–resistant <i>BRCA</i>-mutant (BRCAm) high-grade serous ovarian cancer (HGSOC) represents a new clinical challenge with unmet therapeutic needs. Here, we performed quantitative high-throughput drug combination screen that identified the of an ATR (ATRi) and AKT (AKTi) as effective treatment strategy for both PARPi-sensitive PARPi-resistant BRCAm HGSOC. The ATRi AKTi induced DNA damage R loop–mediated replication stress (RS)....
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