RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer

Liu, Yajing; Burness, Monika L.; Martin-Trevino, Rachel; Guy, Joey; Bai, Shoumei; Harouaka, Ramdane; Brooks, Michael; Li, Shang; Fox, Alexandra; Luther, Tahra; Davis, April; Baker, Trenton L.; Colacino, Justin A.; Clouthier, Shawn G.; Shao, Zhi Ming; Wicha, Max S.; Liu, Suling

doi:10.1158/1078-0432.ccr-15-1348

Cited by 122 publications

(94 citation statements)

References 33 publications

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“…Finally, overexpression of RAD51 recombinase, which carries out the DNA strand exchange reaction at the central step of HR potentiates resistance of the triple negative breast cancer cells to PARP inhibitors (Liu et al, 2016). …”

Section: Lessons From Parp Resistancementioning

confidence: 99%

Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy

Hengel

Spies

2017

Cell Chemical Biology

117

126

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To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop resistance to radiation and DNA damaging chemotherapeutics. Chemical inhibition of the key DNA repair proteins and pharmacologically induced synthetic lethality have become instrumental in both dissecting the complex DNA repair networks and as promising anticancer agents. The difficulty in capitalizing on synthetically lethal interactions in cancer cells is that many potential targets do not possess well-defined small molecule binding determinates. In this review we will discuss several successful campaigns to identify and leverage small-molecule inhibitors of the DNA repair proteins, from PARP1, a paradigm case for clinically successful small molecule inhibitors, to coveted new targets, such as RAD51 recombinase, RAD52 DNA repair protein, MRE11 nuclease and WRN DNA helicase.

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Section: Lessons From Parp Resistancementioning

confidence: 99%

Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy

Hengel

Spies

2017

Cell Chemical Biology

117

126

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“…Accumulating evidence shows that cancer stem cells (CSCs) are responsible for the resistance to chemotherapeutic agents [6], but it is unknown whether targeted therapy (including PARP inhibition) has the same effect. As reported in the paper entitled “RAD51 mediates resistance of cancer stem cells to PARP inhibition in triple-negative breast cancer” [7] in a recent issue of Clinical Cancer Research , we found that PARP inhibitor (PARPi) only effectively targets BRCA1 -mutant bulk tumor cells and RAD51 , a gene involved in DNA double-strand break repair [8], mediates this process, but BRCA1 -wild-type cancer cells and BRCA1 -mutant CSCs are resistant to PARP inhibition. RAD51 knockdown (KD) sensitizes both BRCA1 -mutant CSCs and BRCA1 -wild-type cells to PARP inhibition.…”

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confidence: 99%

Rad51 inhibition sensitizes breast cancer stem cells to PARP inhibitor in triple-negative breast cancer

Wang

Liu

2017

Chin J Cancer

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“…Cancer stem cells (CSCs) are defined as a small subpopulation of cancer cells with the ability of self-renewal and pluripotency, and they are therefore responsible for poor prognosis in patients by promoting tumor recurrence and metastasis. 4,5 The plasticity of CSCs may be regulated by factors in the tumor microenvironment. 6,7 However, the effect of the tumor microenvironment on the stemness of cancer cells remains unclear in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

IL‐10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF‐κB/Notch1 pathway in non‐small cell lung cancer

Dong

et al. 2019

Intl Journal of Cancer

126

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Tumor‐associated macrophages (TAMs), key immune cells in the tumor microenvironment, are shown to be closely correlated with the progression of non‐small cell lung cancer (NSCLC). Cancer stem cells (CSCs) can contribute to NSCLC progression as well. We aimed to clarify whether TAMs promote the progression of NSCLC by mainly affecting the activities of CSCs. We found that TAM‐like cells promoted CSC‐like properties in NSCLC cells in vitro, which was mediated by TAM‐derived IL‐10. TAM‐derived IL‐10 promoted CSC‐like properties of NSCLC cells through JAK1/STAT1/NF‐κB/Notch1 signaling. Blockade of IL‐10/JAK1 signaling inhibited TAM‐mediated NSCLC tumor growth in vivo, and the TAM‐mediated expression of CSC‐related and mesenchymal‐related genes in NSCLC. Lastly, expression levels of these signaling molecules were significantly correlated with survival of NSCLC patients. Therefore, IL‐10/JAK1 signaling might be a potential therapeutic target for NSCLC treatment.

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RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer

Cited by 122 publications

References 33 publications

Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy

Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy

Rad51 inhibition sensitizes breast cancer stem cells to PARP inhibitor in triple-negative breast cancer

IL‐10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF‐κB/Notch1 pathway in non‐small cell lung cancer

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