TY - JOUR
T1 - WEE1 inhibition and genomic instability in cancer
AU - Vriend, Lianne E. M.
AU - de Witt Hamer, Philip C.
AU - van Noorden, Cornelis J. F.
AU - Würdinger, Thomas
PY - 2013
Y1 - 2013
N2 - One of the hallmarks of cancer is genomic instability controlled by cell cycle checkpoints. The G1 and G2 checkpoints allow DNA damage responses, whereas the mitotic checkpoint enables correct seggregation of the sister chromosomes to prevent aneuploidy. Cancer cells often lack a functional G1 arrest and rely on G2 arrest for DNA damage responses. WEE1 kinase is an important regulator of the G2 checkpoint and is overexpressed in various cancer types. Inhibition of WEE1 is a promising strategy in cancer therapy in combination with DNA-damaging agents, especially when cancer cells harbor p53 mutations, as it causes mitotic catastrophy when DNA is not repaired during G2 arrest. Cancer cell response to WEE1 inhibition monotherapy has also been demonstrated in various types of cancer, including p53 wild-type cancers. We postulate that chromosomal instability can explain tumor response to WEE1 monotherapy. Therefore, chromosomal instability may need to be taken into account when determining the most effective strategy for the use of WEE1 inhibitors in cancer therapy
AB - One of the hallmarks of cancer is genomic instability controlled by cell cycle checkpoints. The G1 and G2 checkpoints allow DNA damage responses, whereas the mitotic checkpoint enables correct seggregation of the sister chromosomes to prevent aneuploidy. Cancer cells often lack a functional G1 arrest and rely on G2 arrest for DNA damage responses. WEE1 kinase is an important regulator of the G2 checkpoint and is overexpressed in various cancer types. Inhibition of WEE1 is a promising strategy in cancer therapy in combination with DNA-damaging agents, especially when cancer cells harbor p53 mutations, as it causes mitotic catastrophy when DNA is not repaired during G2 arrest. Cancer cell response to WEE1 inhibition monotherapy has also been demonstrated in various types of cancer, including p53 wild-type cancers. We postulate that chromosomal instability can explain tumor response to WEE1 monotherapy. Therefore, chromosomal instability may need to be taken into account when determining the most effective strategy for the use of WEE1 inhibitors in cancer therapy
U2 - https://doi.org/10.1016/j.bbcan.2013.05.002
DO - https://doi.org/10.1016/j.bbcan.2013.05.002
M3 - Review article
C2 - 23727417
SN - 0304-419X
VL - 1836
SP - 227
EP - 235
JO - BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
JF - BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
IS - 2
ER -