PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes

Over-Expression of PDGFR-β Promotes PDGF-Induced Proliferation, Migration, and Angiogenesis of EPCs through PI3K/Akt Signaling Pathway

(2012) Hang Wang et al.   PLoS One

Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in multiple myeloma

(2011) Philipp Baumann et al.   ANTI-CANCER DRUGS

Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice

(2011) J M García-Martínez et al.   BRITISH JOURNAL OF CANCER

Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells

(2011) Euphemia Leung et al.   CANCER BIOLOGY & THERAPY

Co-administration of perifosine with paclitaxel synergistically induces apoptosis in ovarian cancer cells: More than just AKT inhibition

(2011) Hui Sun et al.   CANCER LETTERS

Akt signalling in health and disease

(2011) Ingeborg Hers et al.   CELLULAR SIGNALLING

Combination of Farnesyltransferase and Akt Inhibitors Is Synergistic in Breast Cancer Cells and Causes Significant Breast Tumor Regression in ErbB2 Transgenic Mice

(2011) M. E. Balasis et al.   CLINICAL CANCER RESEARCH

Antitumor Activity of NVP-BKM120--A Selective Pan Class I PI3 Kinase Inhibitor Showed Differential Forms of Cell Death Based on p53 Status of Glioma Cells

(2011) D. Koul et al.   CLINICAL CANCER RESEARCH

Dual Targeting of Phosphoinositide 3-Kinase and Mammalian Target of Rapamycin Using NVP-BEZ235 as a Novel Therapeutic Approach in Human Ovarian Carcinoma

(2011) C. Santiskulvong et al.   CLINICAL CANCER RESEARCH

Novel Phosphoinositide 3-Kinase/mTOR Dual Inhibitor, NVP-BGT226, Displays Potent Growth-Inhibitory Activity against Human Head and Neck Cancer Cells In Vitro and In Vivo

(2011) K.-Y. Chang et al.   CLINICAL CANCER RESEARCH

Antitumor Efficacy of PKI-587, a Highly Potent Dual PI3K/mTOR Kinase Inhibitor

(2011) R. Mallon et al.   CLINICAL CANCER RESEARCH

Targeting the mTOR kinase domain: the second generation of mTOR inhibitors

(2011) Yan-Jie Zhang et al.   DRUG DISCOVERY TODAY

Insulin receptor and cancer

(2011) A. Belfiore et al.   ENDOCRINE-RELATED CANCER

The efficacy of a novel, dual PI3K/mTOR inhibitor NVP-BEZ235 to enhance chemotherapy and antiangiogenic response in pancreatic cancer

(2011) Niranjan Awasthi et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

The Akt-Specific Inhibitor MK2206 Selectively Inhibits Thyroid Cancer Cells Harboring Mutations That Can Activate the PI3K/Akt Pathway

(2011) Ruixin Liu et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

GDC-0941 Inhibits Metastatic Characteristics of Thyroid Carcinomas by Targeting both the Phosphoinositide-3 Kinase (PI3K) and Hypoxia-Inducible Factor-1α (HIF-1α) Pathways

(2011) Natalie Burrows et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Perifosine Plus Bortezomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma Previously Treated With Bortezomib: Results of a Multicenter Phase I/II Trial

(2011) Paul G. Richardson et al.   JOURNAL OF CLINICAL ONCOLOGY

Randomized Placebo-Controlled Phase II Trial of Perifosine Plus Capecitabine As Second- or Third-Line Therapy in Patients With Metastatic Colorectal Cancer

(2011) Johanna C. Bendell et al.   JOURNAL OF CLINICAL ONCOLOGY

First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors

(2011) Timothy A. Yap et al.   JOURNAL OF CLINICAL ONCOLOGY

Discovery of a Potent, Selective, and Orally Available Class I Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor (GDC-0980) for the Treatment of Cancer

(2011) Daniel P. Sutherlin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Autophagy suppression promotes apoptotic cell death in response to inhibition of the PI3K—mTOR pathway in pancreatic adenocarcinoma

(2011) Olga K. Mirzoeva et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

Activation of Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Mediates Acquired Resistance to Sorafenib in Hepatocellular Carcinoma Cells

(2011) K.-F. Chen et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Disruption of the AKT pathway inhibits metastasis in an orthotopic model of head and neck squamous cell carcinoma

(2011) Joseph A. Knowles et al.   LARYNGOSCOPE

Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in combination with sorafenib

(2011) Didier Roulin et al.   Molecular Cancer

GDC-0980 Is a Novel Class I PI3K/mTOR Kinase Inhibitor with Robust Activity in Cancer Models Driven by the PI3K Pathway

(2011) J. J. Wallin et al.   MOLECULAR CANCER THERAPEUTICS

MK-2206, a Novel Allosteric Inhibitor of Akt, Synergizes with Gefitinib against Malignant Glioma via Modulating Both Autophagy and Apoptosis

(2011) Y. Cheng et al.   MOLECULAR CANCER THERAPEUTICS

Perifosine and CCI 779 Co-Operate to Induce Cell Death and Decrease Proliferation in PTEN-Intact and PTEN-Deficient PDGF-Driven Murine Glioblastoma

(2011) Kenneth L. Pitter et al.   PLoS One

The Combination of RAD001 and NVP-BEZ235 Exerts Synergistic Anticancer Activity against Non-Small Cell Lung Cancer In Vitro and In Vivo

(2011) Cheng-Xiong Xu et al.   PLoS One

The Dual PI3K/mTOR Inhibitor NVP-BEZ235 Induces Tumor Regression in a Genetically Engineered Mouse Model of PIK3CA Wild-Type Colorectal Cancer

(2011) Jatin Roper et al.   PLoS One

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer

(2011) Matthew T. Burger et al.   ACS Medicinal Chemistry Letters

Potential involvement of F0F1-ATP(synth)ase and reactive oxygen species in apoptosis induction by the antineoplastic agent erucylphosphohomocholine in glioblastoma cell lines

(2010) Leo Veenman et al.   APOPTOSIS

Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas

(2010) A. P. Bhatt et al.   BLOOD

The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer

(2010) Carlos A. Castaneda et al.   CANCER AND METASTASIS REVIEWS

Erucylphospho-N,N,N-trimethylpropylammonium (erufosine) is a potential antimyeloma drug devoid of myelotoxicity

(2010) Deyan Y. Yosifov et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

The PI-3 kinase-Akt-MDM2-survivin signaling axis in high-risk neuroblastoma: a target for PI-3 kinase inhibitor intervention

(2010) Susan K. Peirce et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Compensatory activation of Akt in response to mTOR and Raf inhibitors – A rationale for dual-targeted therapy approaches in neuroendocrine tumor disease

(2010) Kathrin Zitzmann et al.   CANCER LETTERS

The Akt activation inhibitor TCN-P inhibits Akt phosphorylation by binding to the PH domain of Akt and blocking its recruitment to the plasma membrane

(2010) N Berndt et al.   CELL DEATH AND DIFFERENTIATION

Clinical and Translational Studies of a Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia

(2010) I. M. Ghobrial et al.   CLINICAL CANCER RESEARCH

GSK690693 Delays Tumor Onset and Progression in Genetically Defined Mouse Models Expressing Activated Akt

(2010) D. A. Altomare et al.   CLINICAL CANCER RESEARCH

Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma

(2010) S. A. Aziz et al.   CLINICAL CANCER RESEARCH

NVP-BEZ235 as a New Therapeutic Option for Sarcomas

(2010) M. C. Manara et al.   CLINICAL CANCER RESEARCH

Combination Therapy Targeting Both Tumor-Initiating and Differentiated Cell Populations in Prostate Carcinoma

(2010) A. Dubrovska et al.   CLINICAL CANCER RESEARCH

Perifosine induces cell cycle arrest and apoptosis in human hepatocellular carcinoma cell lines by blockade of Akt phosphorylation

(2010) Hong-rong Fei et al.   CYTOTECHNOLOGY

Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 5′-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound26(PKI-587), a Highly Efficacious Dual Inhibitor

(2010) Aranapakam M. Venkatesan et al.   JOURNAL OF MEDICINAL CHEMISTRY

In Vitro and In Vivo Inhibition of Neuroblastoma Tumor Cell Growth by AKT Inhibitor Perifosine

(2010) Z. Li et al.   JNCI-Journal of the National Cancer Institute

Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms

(2010) A M Martelli et al.   LEUKEMIA

Erufosine, a novel alkylphosphocholine, induces apoptosis in CLL through a caspase-dependent pathway

(2010) Sonja Katharina Königs et al.   LEUKEMIA RESEARCH

Antitumor Efficacy Profile of PKI-402, a Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor

(2010) Robert Mallon et al.   MOLECULAR CANCER THERAPEUTICS

MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor Efficacy by Standard Chemotherapeutic Agents or Molecular Targeted Drugs In vitro and In vivo

(2010) H. Hirai et al.   MOLECULAR CANCER THERAPEUTICS

The emerging mechanisms of isoform-specific PI3K signalling

(2010) Bart Vanhaesebroeck et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma

(2010) D. Koul et al.   NEURO-ONCOLOGY

Activated MEK cooperates with Ink4a/Arf loss or Akt activation to induce gliomas in vivo

(2010) J P Robinson et al.   ONCOGENE

Initial testing (stage 1) of the Akt inhibitor GSK690693 by the pediatric preclinical testing program

(2010) Hernan Carol et al.   PEDIATRIC BLOOD & CANCER

Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo

(2010) Jieru Meng et al.   PLoS One

The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation

(2010) Justine Rudner et al.   Radiation Oncology

Nuclear Phospho-Akt Increase Predicts Synergy of PI3K Inhibition and Doxorubicin in Breast and Ovarian Cancer

(2010) J. J. Wallin et al.   Science Translational Medicine

The proliferating role of insulin and insulin-like growth factors in cancer

(2010) Emily Jane Gallagher et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

A complex interplay between Akt, TSC2 and the two mTOR complexes: Figure 1

(2009) Jingxiang Huang et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

In vitro evaluation of pan-PI3-kinase inhibitor SF1126 in trastuzumab-sensitive and trastuzumab-resistant HER2-over-expressing breast cancer cells

(2009) Tuba Ozbay et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Antimyeloma Activity of the Orally Bioavailable Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235

(2009) D. W. McMillin et al.   CANCER RESEARCH

Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Blockade Is an Effective Radiosensitizing Strategy for the Treatment of Non-Small Cell Lung Cancer Harboring K-RAS Mutations

(2009) G. Konstantinidou et al.   CANCER RESEARCH

Suppression of HER2/HER3-Mediated Growth of Breast Cancer Cells with Combinations of GDC-0941 PI3K Inhibitor, Trastuzumab, and Pertuzumab

(2009) E. Yao et al.   CLINICAL CANCER RESEARCH

PIKKing on PKB: regulation of PKB activity by phosphorylation

(2009) Lana Bozulic et al.   CURRENT OPINION IN CELL BIOLOGY

Lead Optimization of N-3-Substituted 7-Morpholinotriazolopyrimidines as Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of PKI-402

(2009) Christoph M. Dehnhardt et al.   JOURNAL OF MEDICINAL CHEMISTRY

Phosphatidylinositol-3-Kinase/Akt Signaling Pathway and Kidney Cancer, and the Therapeutic Potential of Phosphatidylinositol-3-Kinase/Akt Inhibitors

(2009) Camillo Porta et al.   JOURNAL OF UROLOGY

The Alkylphospholipid Perifosine Induces Apoptosis and p21-Mediated Cell Cycle Arrest in Medulloblastoma

(2009) A. Kumar et al.   MOLECULAR CANCER RESEARCH

Targeting Melanoma with Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors

(2009) R. Marone et al.   MOLECULAR CANCER RESEARCH

Peroxisome proliferator-activated receptor   agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity

(2009) N. T. Ihle et al.   MOLECULAR CANCER THERAPEUTICS

NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas

(2009) T.-J. Liu et al.   MOLECULAR CANCER THERAPEUTICS

Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941

(2009) F. I. Raynaud et al.   MOLECULAR CANCER THERAPEUTICS

The Role of IGF-1R in Pediatric Malignancies

(2009) S. Y. Kim et al.   ONCOLOGIST

Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells

(2009) Saskia M. Brachmann et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Roles of PI3-K/Akt pathways in nanoparticle realgar powders-induced apoptosis in U937 cells

(2008) Rong-gang XI et al.   ACTA PHARMACOLOGICA SINICA

PTEN and the PI3-Kinase Pathway in Cancer

(2008) Nader Chalhoub et al.   Annual Review of Pathology-Mechanisms of Disease

Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway

(2008) Frédéric Stauffer et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines

(2008) D. S. Levy et al.   BLOOD

Perifosine induces differentiation and cell death in prostate cancer cells

(2008) Daniel Floryk et al.   CANCER LETTERS

NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations

(2008) V. Serra et al.   CANCER RESEARCH

Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity

(2008) N. Rhodes et al.   CANCER RESEARCH

The Type 1 Insulin-Like Growth Factor Receptor Pathway

(2008) M. M. Chitnis et al.   CLINICAL CANCER RESEARCH

Perifosine inhibits growth of human experimental endometrial cancers by blockade of AKT phosphorylation

(2008) Jörg B. Engel et al.   European Journal of Obstetrics & Gynecology and Reproductive Biology

The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma

(2008) Philipp Baumann et al.   EXPERIMENTAL CELL RESEARCH

Identification of 4-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a Novel Inhibitor of AKT Kinase

(2008) Dirk A. Heerding et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Identification of 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer†

(2008) Adrian J. Folkes et al.   JOURNAL OF MEDICINAL CHEMISTRY

Activation of Akt as a Mechanism for Tumor Immune Evasion

(2008) Kyung Hee Noh et al.   MOLECULAR THERAPY

The p110  isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110 

(2008) J. Guillermet-Guibert et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Protein and lipid kinase inhibitors as targeted anticancer agents of the Ras/Raf/MEK and PI3K/PKB pathways

(2008) Carlos García-Echeverría   Purinergic Signalling