DNA repair dysregulation from cancer driver to therapeutic target

2012 ◽  
Vol 12 (12) ◽  
pp. 801-817 ◽  
Author(s):  
Nicola J. Curtin
Keyword(s):  
Dna Repair ◽  
Therapeutic Target ◽  
Cancer Driver

scholarly journals Cyclin-Dependent Kinase 2 Functions in Normal DNA Repair and Is a Therapeutic Target in BRCA1-Deficient Cancers

2006 ◽  
Vol 66 (16) ◽  
pp. 8219-8226 ◽  
Author(s):  
Andrew J. Deans ◽  
Kum Kum Khanna ◽  
Carolyn J. McNees ◽  
Ciro Mercurio ◽  
Jörg Heierhorst ◽  
...  
Keyword(s):  
Dna Repair ◽  
Therapeutic Target ◽  
Cyclin Dependent Kinase

Abstract 2827: Alternative non-homologous end joining DNA repair as therapeutic target in multiple myeloma

2018 ◽  
Author(s):  
Daniele Caracciolo ◽  
Martina Montesano ◽  
Emanuela Altomare ◽  
Grazia Consolo ◽  
Nicola Amodio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dna Repair ◽  
Therapeutic Target ◽  
End Joining ◽  
Non Homologous End Joining

Abstract 2723: Defective homologous recombination DNA repair as therapeutic target in advanced chordoma

2019 ◽  
Author(s):  
Stefan Gröschel ◽  
Daniel Hübschmann ◽  
Francesco Raimondi ◽  
Peter Horak ◽  
Gregor Warsow ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Therapeutic Target

scholarly journals Defective homologous recombination DNA repair as therapeutic target in advanced chordoma

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Stefan Gröschel ◽  
Daniel Hübschmann ◽  
Francesco Raimondi ◽  
Peter Horak ◽  
Gregor Warsow ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Therapeutic Target

scholarly journals microRNA-17~92 is a powerful cancer driver and a therapeutic target

Cell Cycle ◽  
2014 ◽  
Vol 13 (4) ◽  
pp. 495-496 ◽  
Author(s):  
Hyun Yong Jin ◽  
Maoyi Lai ◽  
Changchun Xiao
Keyword(s):  
Therapeutic Target ◽  
Cancer Driver

scholarly journals DNA Repair: From Genome Maintenance to Biomarker and Therapeutic Target

2011 ◽  
Vol 17 (22) ◽  
pp. 6973-6984 ◽  
Author(s):  
Shadia Jalal ◽  
Jennifer N. Earley ◽  
John J. Turchi
Keyword(s):  
Dna Repair ◽  
Therapeutic Target ◽  
Genome Maintenance

scholarly journals PRMT1 Confers Resistance to Olaparib via Modulating MYC Signaling in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 (10) ◽  
pp. 1009
Author(s):  
Wen-Jing Hsu ◽  
Cheng-Hsun Chen ◽  
Yu-Chu Chang ◽  
Chia-Hsiung Cheng ◽  
Ying-Huei TsaI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Protein Stability ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Target ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Bioinformatic Analysis ◽  
Parp Inhibitors ◽  
Methyl Transferase

Treatment of triple-negative breast cancer (TNBC) remains an unmet clinical need owing to its lack of an efficient therapeutic target. The targeting of DNA repair by poly(ADP-ribose) polymerase (PARP) inhibitors has shown benefit for patients with the BRCA variation. However, sensitivities to the PARP inhibitors were reported regardless of BRCA status. Thus, exploring the underlying mechanisms is imperative. Herein, we identified that breast cancer cells with an elevated expression of protein arginine methyl transferase 1 (PRMT1) was associated with therapeutic sensitivity to the PARP inhibitor olaparib. The results of cell viability and colony formation assays indicated that the suppression of PRMT1 by small hairpin RNA or by the chemical inhibitor increased sensitivity to olaparib in human TNBC MDA-MB-231 and BT549 cells. Bioinformatic analysis revealed that PRMT1 expression was significantly associated with the MYC signature, and TNBC cells with higher PRMT1 and the MYC signature were associated with therapeutic sensitivity to olaparib. Mechanistic studies further demonstrated that knockdown of PRMT1 reduced the c-Myc protein level and downregulated the expression of MYC downstream targets, whereas overexpression of PRMT1 enhanced c-Myc protein expression. Moreover, the overexpression of PRMT1 promoted c-Myc protein stability, and the inhibition of PRMT1 downregulated c-Myc protein stability. Accordingly, the knockdown of PRMT1 inhibited homologous recombination gene expression. These data indicate that PRMT1 is instrumental in regulating DNA repair, at least in part, by modulating c-Myc signaling. Our data highlighted the PRMT1/c-Myc network as a potential therapeutic target in patients with TNBC.

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