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CRISPR/Cas9-induced saturated mutagenesis identifies Rad51 haplotype as a marker of PARP inhibitor sensitivity in breast cancer

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机构: [1]Hebei Univ,Affiliated Hosp,Dept Med Oncol,Hebei Key Lab Canc Radiotherapy & Chemotherapy,212 Yuhua East Rd,Baoding 071000,Hebei,Peoples R China
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关键词: PARP inhibitor CRISPR Cas9 Rad51 haplotype breast cancer

摘要:
Breast cancer treatment with poly(ADP-ribose)polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination repair (HRR) pathway. The chemical inhibition of many HRR deficiency genes may sensitize cancer cells to PARP inhibitors. In the present study, Rad51, a central player in the HRR pathway, was selected to explore additional low variation and highly representative markers for PARP inhibitor activity. A CRISPR/Cas9-based saturated mutation approach for the Rad51 WALKER domain was used to evaluate the sensitivity of the PARP inhibitor olaparib. Five amino acid mutation sites were identified in olaparib-resistant cells. Two Rad51 haplotypes were assembled from the mutations, and may represent useful pharmacogenomic markers of PARP inhibitor sensitivity.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 4 区 医学:研究与实验 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验 4 区 肿瘤学
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出版当年[2022]版:
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Q3 ONCOLOGY
最新[2023]版:
Q2 MEDICINE, RESEARCH & EXPERIMENTAL Q2 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

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第一作者机构: [1]Hebei Univ,Affiliated Hosp,Dept Med Oncol,Hebei Key Lab Canc Radiotherapy & Chemotherapy,212 Yuhua East Rd,Baoding 071000,Hebei,Peoples R China
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通讯机构: [1]Hebei Univ,Affiliated Hosp,Dept Med Oncol,Hebei Key Lab Canc Radiotherapy & Chemotherapy,212 Yuhua East Rd,Baoding 071000,Hebei,Peoples R China [*1]Department ofMedical Oncology,Affiliated Hospital of Hebei University,HebeiKey Laboratory of Cancer Radiotherapy and Chemotherapy,212 Yuhua East Road,Baoding,Hebei 071000,P.R. China
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