Fig. 4
From: A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target
Mechanism of action of WEE1/PKMYT1 inhibitors for the treatment of cancer cells. a Schematic representation of WEE1/PKMYT1 inhibition as monotherapy. In cancer cells, oncogenes promote high rate of proliferation, replication stress and the over-expression of WEE1/PKMYT1 kinases. In this scenario, cancer cells need WEE1 and PKMYT1 to sustain replication stress and proliferation. The inhibition of WEE1/PKMYT1 results in the accumulation of DNA damages, the increase of genetic instability and induction of apoptosis. b Schematic representation of WEE1/PKMYT1 inhibition in combination with DNA damaging agents. Cancer cells respond to DNA damages by activating WEE1/PKMYT1 kinases. The inhibition of WEE1/PKMYT1 enhances the cytotoxicity of DNA damaging agents by inhibiting DNA repair and promoting cell cycle progression even in the presence of DNA damages. Therefore, cancer cells accumulate massive DNA damages until a point of no return