PARP inhibition increases PI3K/mTOR pathway activity through LKB1 inactivation <i>in vitro</i>.

<p>(A) Hierarchical clustering of proteins identified in lysates from SCLC cell lines (H69, H82, H841) treated with vehicle or olaparib for 24 hours revealed increased activity of the PI3K/mTOR pathway following PARP inhibition (FDR≤0.1, equivalent p-value≤0.037). (B) Individual phosphorylated proteins in the PI3K/mTOR pathway (p-mTor, p-AKT and p-S6 kinase) are increased following treatment with either olaparib or rucaparib (p≤0.02). (C) Lysates from cell lines treated with olaparib or rucaparib versus vehicle for 24 hours show inactivation of the LKB1 pathway (LKB1, pAMPKα, and pTSC2; p≤0.042).