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Pregled bibliografske jedinice broj: 769159

A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer

Dietlein, F.; Kalb, B.; Jokić, Mladen; Noll, E.M.; Strong, A.; Tharun, L.; Ozretić, Luka; Künstlinger, H.; Kambartel, K.; Randerath, W.J. et al.
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer // Cell, 162 (2015), 1; 146-159 doi:10.1016/j.cell.2015.05.053 (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 769159 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer

Autori
Dietlein, F. ; Kalb, B. ; Jokić, Mladen ; Noll, E.M. ; Strong, A. ; Tharun, L. ; Ozretić, Luka ; Künstlinger, H. ; Kambartel, K. ; Randerath, W.J. ; Jüngst, C. ; Schmitt, A. ; Torgovnick, A. ; Richters, A. ; Rauh, D. ; Siedek, F. ; Persigehl, T. ; Mauch, C. ; Bartkova, J. ; Bradley, A. ; Sprick, M.R. ; Trumpp, A. ; Rad, R. ; Saur, D. ; Bartek, J. ; Wolf, J. ; Büttner, R. ; Thomas, R.K. ; Reinhardt, H.C.

Izvornik
Cell (0092-8674) 162 (2015), 1; 146-159

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
synergism; Chk-1; MK2; Kras; cancer

Sažetak
KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint- abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. Mechanistically, we show that KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity. We demonstrate that simultaneous Chk1- and MK2 inhibition leads to mitotic catastrophe in KRAS-mutant cells. This actionable synergistic interaction is validated using xenograft models, as well as distinct Kras- or Braf-driven autochthonous murine cancer models. Lastly, we show that combined checkpoint inhibition induces apoptotic cell death in KRAS- or BRAF-mutant tumor cells directly isolated from patients. These results strongly recommend simultaneous Chk1- and MK2 inhibition as a therapeutic strategy for the treatment of KRAS- or BRAF-driven cancers.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA

Profili:

Avatar Url Mladen Jokić (autor)

Poveznice na cjeloviti tekst rada:

doi www.sciencedirect.com

Citiraj ovu publikaciju:

Dietlein, F.; Kalb, B.; Jokić, Mladen; Noll, E.M.; Strong, A.; Tharun, L.; Ozretić, Luka; Künstlinger, H.; Kambartel, K.; Randerath, W.J. et al.
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer // Cell, 162 (2015), 1; 146-159 doi:10.1016/j.cell.2015.05.053 (međunarodna recenzija, članak, znanstveni)
Dietlein, F., Kalb, B., Jokić, M., Noll, E., Strong, A., Tharun, L., Ozretić, L., Künstlinger, H., Kambartel, K. & Randerath, W. (2015) A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer. Cell, 162 (1), 146-159 doi:10.1016/j.cell.2015.05.053.
@article{article, author = {Dietlein, F. and Kalb, B. and Joki\'{c}, Mladen and Noll, E.M. and Strong, A. and Tharun, L. and Ozreti\'{c}, Luka and K\"{u}nstlinger, H. and Kambartel, K. and Randerath, W.J. and J\"{u}ngst, C. and Schmitt, A. and Torgovnick, A. and Richters, A. and Rauh, D. and Siedek, F. and Persigehl, T. and Mauch, C. and Bartkova, J. and Bradley, A. and Sprick, M.R. and Trumpp, A. and Rad, R. and Saur, D. and Bartek, J. and Wolf, J. and B\"{u}ttner, R. and Thomas, R.K. and Reinhardt, H.C.}, year = {2015}, pages = {146-159}, DOI = {10.1016/j.cell.2015.05.053}, keywords = {synergism, Chk-1, MK2, Kras, cancer}, journal = {Cell}, doi = {10.1016/j.cell.2015.05.053}, volume = {162}, number = {1}, issn = {0092-8674}, title = {A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer}, keyword = {synergism, Chk-1, MK2, Kras, cancer} }
@article{article, author = {Dietlein, F. and Kalb, B. and Joki\'{c}, Mladen and Noll, E.M. and Strong, A. and Tharun, L. and Ozreti\'{c}, Luka and K\"{u}nstlinger, H. and Kambartel, K. and Randerath, W.J. and J\"{u}ngst, C. and Schmitt, A. and Torgovnick, A. and Richters, A. and Rauh, D. and Siedek, F. and Persigehl, T. and Mauch, C. and Bartkova, J. and Bradley, A. and Sprick, M.R. and Trumpp, A. and Rad, R. and Saur, D. and Bartek, J. and Wolf, J. and B\"{u}ttner, R. and Thomas, R.K. and Reinhardt, H.C.}, year = {2015}, pages = {146-159}, DOI = {10.1016/j.cell.2015.05.053}, keywords = {synergism, Chk-1, MK2, Kras, cancer}, journal = {Cell}, doi = {10.1016/j.cell.2015.05.053}, volume = {162}, number = {1}, issn = {0092-8674}, title = {A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer}, keyword = {synergism, Chk-1, MK2, Kras, cancer} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE
  • Nature Index

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