Projects funded by the NCN

Information on the principal investigator and host institution

Information of the project and the call

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The use of olaparib and ATR / CHK1 kinase inhibitors as a targeted anti-cancer therapy based on synthetic lethality

2019/34/E/NZ7/00056

Keywords:

ATR inhibitor CHK1 inhibitor DNA damage response drug resistance homologous recombination olaparib ovarian cancer

Descriptors:

  • NZ7_12: Prevention of human diseases
  • NZ7_14: Pharmacy, pharmacotherapy, pharmacology
  • NZ1_1: Molecular biology

Panel:

NZ7 - Diagnostic tools, therapies and public health: public health, epidemiology, environmental health risks and occupational medicine, medical ethics, drug discovery and therapies, pharmacology

Host institution :

Uniwersytet Łódzki, Wydział Biologii i Ochrony Środowiska

woj.

Other projects carried out by the institution 

Principal investigator (from the host institution):

dr hab. Aneta Katarzyna Rogalska 

Number of co-investigators in the project: 8

Call: SONATA BIS 9 - announced on 2019-06-17

Amount awarded: 1 999 020 PLN

Project start date (Y-m-d): 2020-07-01

Project end date (Y-m-d): 2025-06-30

Project duration:: 60 months (the same as in the proposal)

Project status: Pending project

Project description

Download the project description in a pdf file

Note - project descriptions were prepared by the authors of the applications themselves and placed in the system in an unchanged form.

Information in the final report

  • Publication in academic press/journals (22)
  1. Molecular mechanisms restoring olaparib efficacy through ATR/CHK1 pathway inhibition in olaparib-resistant BRCA1/2MUT ovarian Cancer models.
    Authors:
    Biegała Ł, Statkiewicz M, Gajek A, Szymczak-Pajor I, Rusetska N, Śliwińska A, Marczak A, Mikula M, Rogalska A.
    Academic press:
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (rok: 2024, tom: 2, strony: 45676), Wydawca: Nature
    Status:
    Published
    DOI:
    10.1016/j.bbadis.2024.167574 - link to the publication
  2. PARP inhibitor resistance in ovarian cancer: Underlying mechanisms and therapeutic approaches targeting the ATR/CHK1 pathway.
    Authors:
    Biegala, L.; Gajek, A.; Marczak, A.; Rogalska, A.
    Academic press:
    Biochimica et Biophysica Acta - Reviews on Cancer (rok: 2021, tom: 1876, strony: 45673), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bbcan.2021.188633 - link to the publication
  3. PARP Inhibition Increases the Reliance on ATR/CHK1 Checkpoint Signaling Leading to Synthetic Lethality-An Alternative Treatment Strategy for Epithelial Ovarian Cancer Cells Independent from HR Effectiveness
    Authors:
    Gralewska, P.; Gajek, A.; Marczak, A.; Mikula, M.; Ostrowski, J.; Sliwinska, A.; Rogalska, A.
    Academic press:
    International Journal of Molecular Sciences (rok: 2020, tom: 21, strony: 45677), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/ijms21249715 - link to the publication
  4. The Influence of PARP, ATR, CHK1 Inhibitors on Premature Mitotic Entry and Genomic Instability in High-Grade Serous BRCAMUT and BRCAWT Ovarian Cancer Cells
    Authors:
    Gralewska P.; Gajek A.; Rybaczek D.; Marczak A.; Rogalska A.
    Academic press:
    Cells (rok: 2022, tom: 11, strony: 45681), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cells11121889 - link to the publication
  5. Targeted inhibition of the ATR/CHK1 pathway overcomes resistance to olaparib and dysregulates DNA damage response protein expression in BRCA2MUT ovarian cancer cells.
    Authors:
    Biegała Ł, Gajek A, Szymczak-Pajor I, Marczak A, Śliwińska A, Rogalska A.
    Academic press:
    Scientific Reports (rok: 2023, tom: 13, strony: 45673), Wydawca: Nature
    Status:
    Published
    DOI:
    10.1038/s41598-023-50151-y - link to the publication
  6. Targeted Nanocarrier-Based Drug Delivery Strategies for Improving the Therapeutic Efficacy of PARP Inhibitors against Ovarian Cancer
    Authors:
    Gralewska P, Gajek A, Marczak A, Rogalska A.
    Academic press:
    International Journal of Molecular Sciences (rok: 2024, tom: 25, strony: 45686), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/ijms25158304 - link to the publication
  7. The Influence of PARP, ATR, CHK1 Inhibitors on Premature Mitotic Entry and Genomic Instability in High-Grade Serous BRCAMUT and BRCAWT Ovarian Cancer Cells
    Authors:
    Gralewska P.; Gajek A.; Rybaczek D.; Marczak A.; Rogalska A.
    Academic press:
    Cells (rok: 2022, tom: 11, strony: 45681), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cells11121889 - link to the publication
  8. Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors.
    Authors:
    Biegała Ł, Kołat D, Gajek A, Płuciennik E, Marczak A, Śliwińska A, Mikula M, Rogalska A.
    Academic press:
    Cells (rok: 2024, tom: 13, strony: 45688), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cells13100867 - link to the publication
  9. PARP Inhibition Increases the Reliance on ATR/CHK1 Checkpoint Signaling Leading to Synthetic Lethality-An Alternative Treatment Strategy for Epithelial Ovarian Cancer Cells Independent from HR Effectiveness
    Authors:
    Gralewska, P.; Gajek, A.; Marczak, A.; Mikula, M.; Ostrowski, J.; Sliwinska, A.; Rogalska, A.
    Academic press:
    International Journal of Molecular Sciences (rok: 2020, tom: 21, strony: 45677), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/ijms21249715 - link to the publication
  10. Current Implications of microRNAs in Genome Stability and Stress Responses of Ovarian Cancer.
    Authors:
    Gajek, A.; Gralewska, P.; Marczak, A.; Rogalska, A.
    Academic press:
    Cancers (rok: 2021, tom: 13, strony: 45679), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cancers13112690 - link to the publication
  11. PARP Inhibition Increases the Reliance on ATR/CHK1 Checkpoint Signaling Leading to Synthetic Lethality-An Alternative Treatment Strategy for Epithelial Ovarian Cancer Cells Independent from HR Effectiveness
    Authors:
    Gralewska, P.; Gajek, A.; Marczak, A.; Mikula, M.; Ostrowski, J.; Sliwinska, A.; Rogalska, A.
    Academic press:
    International Journal of Molecular Sciences (rok: 2020, tom: 21, strony: 45677), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/ijms21249715 - link to the publication
  12. PARP inhibitor resistance in ovarian cancer: Underlying mechanisms and therapeutic approaches targeting the ATR/CHK1 pathway.
    Authors:
    Biegala, L.; Gajek, A.; Marczak, A.; Rogalska, A.
    Academic press:
    Biochimica et Biophysica Acta - Reviews on Cancer (rok: 2021, tom: 1876, strony: 45673), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bbcan.2021.188633 - link to the publication
  13. PARP inhibitor resistance in ovarian cancer: Underlying mechanisms and therapeutic approaches targeting the ATR/CHK1 pathway.
    Authors:
    Biegala, L.; Gajek, A.; Marczak, A.; Rogalska, A.
    Academic press:
    Biochimica et Biophysica Acta - Reviews on Cancer (rok: 2021, tom: 1876, strony: 45673), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bbcan.2021.188633 - link to the publication
  14. Current Implications of microRNAs in Genome Stability and Stress Responses of Ovarian Cancer.
    Authors:
    Gajek, A.; Gralewska, P.; Marczak, A.; Rogalska, A.
    Academic press:
    Cancers (rok: 2021, tom: 13, strony: 45679), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cancers13112690 - link to the publication
  15. Olaparib-Resistant BRCA2MUT Ovarian Cancer Cells with Restored BRCA2 Abrogate Olaparib-Induced DNA Damage and G2/M Arrest Controlled by the ATR/CHK1 Pathway for Survival
    Authors:
    Biegała, Ł.; Gajek, A.; Marczak, A.; Rogalska, A.
    Academic press:
    Cells (rok: 2023, tom: 12, strony: 13881), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cells12071038 - link to the publication
  16. Current Implications of microRNAs in Genome Stability and Stress Responses of Ovarian Cancer.
    Authors:
    Gajek, A.; Gralewska, P.; Marczak, A.; Rogalska, A.
    Academic press:
    Cancers (rok: 2021, tom: 13, strony: 45679), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cancers13112690 - link to the publication
  17. Current Implications of microRNAs in Genome Stability and Stress Responses of Ovarian Cancer.
    Authors:
    Gajek, A.; Gralewska, P.; Marczak, A.; Rogalska, A.
    Academic press:
    Cancers (rok: 2021, tom: 13, strony: 45679), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cancers13112690 - link to the publication
  18. Targeted inhibition of the ATR/CHK1 pathway overcomes resistance to olaparib and dysregulates DNA damage response protein expression in BRCA2MUT ovarian cancer cells.
    Authors:
    Biegała Ł, Gajek A, Szymczak-Pajor I, Marczak A, Śliwińska A, Rogalska A.
    Academic press:
    Scientific Reports (rok: 2023, tom: 13, strony: 45673), Wydawca: Nature
    Status:
    Published
    DOI:
    10.1038/s41598-023-50151-y - link to the publication
  19. Olaparib-Resistant BRCA2MUT Ovarian Cancer Cells with Restored BRCA2 Abrogate Olaparib-Induced DNA Damage and G2/M Arrest Controlled by the ATR/CHK1 Pathway for Survival
    Authors:
    Biegała, Ł.; Gajek, A.; Marczak, A.; Rogalska, A.
    Academic press:
    Cells (rok: 2023, tom: 12, strony: 13881), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cells12071038 - link to the publication
  20. PARP Inhibition Increases the Reliance on ATR/CHK1 Checkpoint Signaling Leading to Synthetic Lethality-An Alternative Treatment Strategy for Epithelial Ovarian Cancer Cells Independent from HR Effectiveness
    Authors:
    Gralewska, P.; Gajek, A.; Marczak, A.; Mikula, M.; Ostrowski, J.; Sliwinska, A.; Rogalska, A.
    Academic press:
    International Journal of Molecular Sciences (rok: 2020, tom: 21, strony: 45677), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/ijms21249715 - link to the publication
  21. The Influence of PARP, ATR, CHK1 Inhibitors on Premature Mitotic Entry and Genomic Instability in High-Grade Serous BRCAMUT and BRCAWT Ovarian Cancer Cells
    Authors:
    Gralewska P.; Gajek A.; Rybaczek D.; Marczak A.; Rogalska A.
    Academic press:
    Cells (rok: 2022, tom: 11, strony: 45681), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cells11121889 - link to the publication
  22. PARP inhibitor resistance in ovarian cancer: Underlying mechanisms and therapeutic approaches targeting the ATR/CHK1 pathway.
    Authors:
    Biegala, L.; Gajek, A.; Marczak, A.; Rogalska, A.
    Academic press:
    Biochimica et Biophysica Acta - Reviews on Cancer (rok: 2021, tom: 1876, strony: 45673), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bbcan.2021.188633 - link to the publication

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