Cristin-resultat-ID: 1931795
Sist endret: 6. september 2021, 21:44
NVI-rapporteringsår: 2021
Vitenskapelig artikkel

Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells

  • Gro Elise Rødland
  • Sissel Hauge
  • Grete Hasvold
  • Lilli Theres Eilertsen Bay
  • Tine Therese Henriksen-Raabe
  • Mrinal Joel
  • mfl.


ISSN 2072-6694
e-ISSN 2072-6694
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2021
Publisert online: 2021
Open Access


Scopus-ID: 2-s2.0-85111164039

Beskrivelse Beskrivelse


Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells


Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.


Gro Elise Rødland

  • Tilknyttet:
    ved Seksjon for cellebiologi ved Oslo universitetssykehus HF

Sissel Hauge

  • Tilknyttet:

Grete Hasvold

  • Tilknyttet:
    ved Seksjon for tumorbiologi ved Oslo universitetssykehus HF

Lilli Theres Eilertsen Bay

  • Tilknyttet:

Tine Therese Henriksen-Raabe

  • Tilknyttet:
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF
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