PIK3CA and neoplasm: However, we show that genomic alterations in the PI3K/AKT signaling pathway leading to constitutive activation, such as those in our models (Figure 1B) [20,23], may combine with G2/M checkpoint defects to help tumor cells survive traversing the cell cycle despite issues with irregular mitoses, highlighting this pathway as a critical dependency and major target for an unexpected reason (Figure 4A,B and Figure 6).