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• W4361944900 abstract "<div>Abstract<p><b>Purpose:</b> Constitutive activation of phosphoinositide 3-kinase (PI3K) occurs frequently in many human tumors via either gene mutation in the p110α catalytic subunit of PI3K or functional loss of tumor suppressor <i>PTEN</i>. Patients with small-cell lung cancer (SCLC) have very poor prognosis and survival rates such that an effective targeted therapy is in strong demand for these patients. In this study, we characterized the highly selective oral PI3K inhibitor, PF-4989216, in preclinical SCLC models to investigate whether targeting the PI3K pathway is an effective targeted therapy option for SCLCs that harbor a <i>PIK3CA</i> mutation.</p><p><b>Experimental Design:</b> A panel of SCLC cell lines with <i>PIK3CA</i> mutation or <i>PTEN</i> loss were treated with PF-4989216 in several <i>in vitro</i> assays, including PI3K pathway signaling, cell viability, apoptosis, cell-cycle progression, and cell transformation. SCLC cell lines that were sensitive <i>in vitro</i> to PF-4989216 were further evaluated by <i>in vivo</i> animal studies to determine the pharmacokinetic/pharmacodynamic relationship and tumor growth inhibition (TGI) by PF-4989216 treatment.</p><p><b>Results:</b> PF-4989216 inhibited PI3K downstream signaling and subsequently led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in SCLCs harboring <i>PIK3CA</i> mutation. In SCLCs with <i>PTEN</i> loss, PF-4989216 also inhibited PI3K signaling but did not induce BCL2-interacting mediator (BIM)-mediated apoptosis nor was there any effect on cell viability or transformation. These results implicate differential tumorigenesis and apoptosis mechanisms in SCLCs harboring <i>PIK3CA</i> mutation versus <i>PTEN</i> loss.</p><p><b>Conclusions:</b> Our results suggest that PF-4989216 is a potential cancer drug candidate for patients with SCLC with <i>PIK3CA</i> mutation but not <i>PTEN</i> loss. <i>Clin Cancer Res; 20(3); 631–43. ©2013 AACR</i>.</p></div>" @default.
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• W4361944900 date "2023-03-31" @default.
• W4361944900 modified "2023-10-14" @default.
• W4361944900 title "Data from Targeting Small Cell Lung Cancer Harboring <i>PIK3CA</i> Mutation with a Selective Oral PI3K Inhibitor PF-4989216" @default.
• W4361944900 doi "https://doi.org/10.1158/1078-0432.c.6521870" @default.
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