Targeting mTOR signaling pathways and related negative feedback loops for the treatment of acute myeloid leukemia

Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells

(2015) Theodosia Teo et al.   CANCER LETTERS

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

(2015) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

MK2206 potentiates cisplatin-induced cytotoxicity and apoptosis through an interaction of inactivated Akt signaling pathway

(2015) Dingqi Sun et al.   UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS

Targeting mTOR for the treatment of AML. New agents and new directions.

(2015) Jessica K. Altman et al.   Oncotarget

Combined autophagy and HDAC inhibition

(2014) Devalingam Mahalingam et al.   Autophagy

Defective endomitosis during megakaryopoiesis leads to thrombocytopenia in Fanca-/- mice

(2014) P. Pawlikowska et al.   BLOOD

PIM and AKT kinase inhibitors show synergistic cytotoxicity in acute myeloid leukaemia that is associated with convergence on mTOR and MCL1 pathways

(2014) Koremu Meja et al.   BRITISH JOURNAL OF HAEMATOLOGY

A phase I and pharmacokinetic study of oral perifosine with different loading schedules in patients with refractory neoplasms

(2014) William D. Figg et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Discovery of 5-(2-(Phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one Derivatives as Potent Mnk2 Inhibitors: Synthesis, SAR Analysis and Biological Evaluation

(2014) Sarah Diab et al.   ChemMedChem

Preclinical and Early Clinical Evaluation of the Oral AKT Inhibitor, MK-2206, for the Treatment of Acute Myelogenous Leukemia

(2014) M. Y. Konopleva et al.   CLINICAL CANCER RESEARCH

Molecular Pathways: Targeting NRAS in Melanoma and Acute Myelogenous Leukemia

(2014) D. B. Johnson et al.   CLINICAL CANCER RESEARCH

Autophagy Is a Survival Mechanism of Acute Myelogenous Leukemia Precursors during Dual mTORC2/mTORC1 Targeting

(2014) J. K. Altman et al.   CLINICAL CANCER RESEARCH

Idelalisib: First Global Approval

(2014) Anthony Markham   DRUGS

Targeting the phosphoinositide 3-kinase pathway in hematologic malignancies

(2014) E. Jabbour et al.   HAEMATOLOGICA

Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells

(2014) Manabu Kaneko et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110α

(2014) Kira Gritsman et al.   JOURNAL OF CLINICAL INVESTIGATION

Dual PI3K/mTOR inhibition shows antileukemic activity in MLL-rearranged acute myeloid leukemia

(2014) N Sandhöfer et al.   LEUKEMIA

Feedbacks and adaptive capabilities of the PI3K/Akt/mTOR axis in acute myeloid leukemia revealed by pathway selective inhibition and phosphoproteome analysis

(2014) J Bertacchini et al.   LEUKEMIA

You eat what you are: autophagy inhibition as a therapeutic strategy in leukemia

(2014) A R Sehgal et al.   LEUKEMIA

Prognostic significance of constitutive phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase phosphorylation in acute myeloid leukemia

(2014) Sanja Prijić et al.   LEUKEMIA & LYMPHOMA

Inhibition of mTOR-Dependent Autophagy Sensitizes Leukemic Cells to Cytarabine-Induced Apoptotic Death

(2014) Mihajlo Bosnjak et al.   PLoS One

Effect of CAL-101, a PI3Kδ inhibitor, on ribosomal rna synthesis and cell proliferation in acute myeloid leukemia cells

(2014) L X T Nguyen et al.   Blood Cancer Journal

Targeting PI3K/Akt/mTOR Signaling in Cancer

(2014) Camillo Porta et al.   Frontiers in Oncology

Development of everolimus, a novel oral mTOR inhibitor, across a spectrum of diseases

(2013) David Lebwohl et al.   Annals of the New York Academy of Sciences

The ULK1 complex

(2013) Pui-Mun Wong et al.   Autophagy

PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma

(2013) P. G. Richardson et al.   BLOOD

Survival and cure of acute myeloid leukaemia in England, 1971-2006: a population-based study

(2013) Anjali Shah et al.   BRITISH JOURNAL OF HAEMATOLOGY

Phase II Study of the Oral MEK Inhibitor Selumetinib in Advanced Acute Myelogenous Leukemia: A University of Chicago Phase II Consortium Trial

(2013) N. Jain et al.   CLINICAL CANCER RESEARCH

Tumor heterogeneity makes AML a “moving target” for detection of residual disease

(2013) W. Zeijlemaker et al.   CYTOMETRY PART B-CLINICAL CYTOMETRY

Perifosine – a new option in treatment of acute myeloid leukemia?

(2013) Janusz Krawczyk et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

The PDK1 master kinase is over-expressed in acute myeloid leukemia and promotes PKC-mediated survival of leukemic blasts

(2013) J. Zabkiewicz et al.   HAEMATOLOGICA

Phase I study of UCN-01 and perifosine in patients with relapsed and refractory acute leukemias and high-risk myelodysplastic syndrome

(2013) Ivana Gojo et al.   INVESTIGATIONAL NEW DRUGS

Regulation of mTORC1 and its impact on gene expression at a glance

(2013) M. Laplante et al.   JOURNAL OF CELL SCIENCE

A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse

(2013) S Park et al.   LEUKEMIA

Activity of the pan-class I phosphoinositide 3-kinase inhibitor NVP-BKM120 in T-cell acute lymphoblastic leukemia

(2013) A Lonetti et al.   LEUKEMIA

A phase I study of decitabine and rapamycin in relapsed/refractory AML

(2013) Jane L. Liesveld et al.   LEUKEMIA RESEARCH

Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies

(2013) Deepa Sampath et al.   LEUKEMIA RESEARCH

Cell cycle-dependent activity of the novel dual PI3K-MTORC1/2 inhibitor NVP-BGT226 in acute leukemia

(2013) Kerstin Kampa-Schittenhelm et al.   Molecular Cancer

Differential Effects of Selective Inhibitors Targeting the PI3K/AKT/mTOR Pathway in Acute Lymphoblastic Leukemia

(2013) Susanne Badura et al.   PLoS One

Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function

(2013) S. Lim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Lys05

(2012) Ravi K. Amaravadi et al.   Autophagy

Targeting oncogenic Ras signaling in hematologic malignancies

(2012) A. F. Ward et al.   BLOOD

Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment

(2012) Z. Zeng et al.   BLOOD

Dual Targeting of the Akt/mTOR Signaling Pathway Inhibits Castration-Resistant Prostate Cancer in a Genetically Engineered Mouse Model

(2012) N. Floc'h et al.   CANCER RESEARCH

Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer

(2012) James S. Duncan et al.   CELL

mTOR Signaling in Growth Control and Disease

(2012) Mathieu Laplante et al.   CELL

An overview of the mTOR pathway as a target in cancer therapy

(2012) Ryan D Gentzler et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia

(2012) Jay P. Patel et al.   NEW ENGLAND JOURNAL OF MEDICINE

Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

(2011) G. M. Dores et al.   BLOOD

Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107)

(2011) Sergio Amadori et al.   BRITISH JOURNAL OF HAEMATOLOGY

Dual mTORC2/mTORC1 Targeting Results in Potent Suppressive Effects on Acute Myeloid Leukemia (AML) Progenitors

(2011) J. K. Altman et al.   CLINICAL CANCER RESEARCH

Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

(2011) Jesús R. Medina et al.   JOURNAL OF MEDICINAL CHEMISTRY

The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia

(2011) L Willems et al.   LEUKEMIA

Autophagy Inhibition Enhances Daunorubicin-Induced Apoptosis in K562 Cells

(2011) Weidong Han et al.   PLoS One

Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1

(2010) Ayaz Najafov et al.   BIOCHEMICAL JOURNAL

Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials

(2010) D. Grimwade et al.   BLOOD

Targeting of Leukemia-Initiating Cells to Develop Curative Drug Therapies: Straightforward but Nontrivial Concept

(2010) P. Valent   CURRENT CANCER DRUG TARGETS

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

mTOR: from growth signal integration to cancer, diabetes and ageing

(2010) Roberto Zoncu et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

FDA Approval Summary: Temsirolimus as Treatment for Advanced Renal Cell Carcinoma

(2010) V. E. Kwitkowski et al.   ONCOLOGIST

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

Rapamycin, the mTOR kinase inhibitor, sensitizes acute myeloid leukemia cells, HL-60 cells, to the cytotoxic effect of arabinozide cytarabine

(2009) Agnieszka Janus et al.   ANTI-CANCER DRUGS

AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer

(2009) Krishna M. Vasudevan et al.   CANCER CELL

PI3K Pathway Activation Mediates Resistance to MEK Inhibitors in KRAS Mutant Cancers

(2009) S. Wee et al.   CANCER RESEARCH

A Phase I Study of the Mammalian Target of Rapamycin Inhibitor Sirolimus and MEC Chemotherapy in Relapsed and Refractory Acute Myelogenous Leukemia

(2009) A. E. Perl et al.   CLINICAL CANCER RESEARCH

Targeting of mTOR is associated with decreased growth and decreased VEGF expression in acute myeloid leukaemia cells

(2009) A. Böhm et al.   EUROPEAN JOURNAL OF CLINICAL INVESTIGATION

Evaluation of in vivo antineoplastic effects of rapamycin in patients with chemotherapy-refractory AML

(2009) Alexandra Boehm et al.   European Journal of Internal Medicine

Targeting the PI3K/AKT/mTOR signaling network in acute myelogenous leukemia

(2009) Alberto M Martelli et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Use of the Pharmacological Inhibitor BX795 to Study the Regulation and Physiological Roles of TBK1 and IκB Kinase ϵ

(2009) Kristopher Clark et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia

(2009) N Gallay et al.   LEUKEMIA

The nuts and bolts of AGC protein kinases

(2009) Laura R. Pearce et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

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

(2008) D. S. Levy et al.   BLOOD

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

(2008) N. Rhodes et al.   CANCER RESEARCH

Small-Molecule Inhibitors of PDK1

(2008) Christian Peifer et al.   ChemMedChem

A Phase 2 Clinical Trial of Deforolimus (AP23573, MK-8669), a Novel Mammalian Target of Rapamycin Inhibitor, in Patients with Relapsed or Refractory Hematologic Malignancies

(2008) D. A. Rizzieri et al.   CLINICAL CANCER RESEARCH

Lack of antileukemic activity of rapamycin in elderly patients with acute myeloid leukemia evolving from a myelodysplastic syndrome

(2008) Fernando Callera et al.   LEUKEMIA RESEARCH

PI3K pathway alterations in cancer: variations on a theme

(2008) T L Yuan et al.   ONCOGENE