Targeting mTOR for the treatment of B cell malignancies

Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

(2016) Andrew W. Roberts et al.   NEW ENGLAND JOURNAL OF MEDICINE

A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma

(2015) Johanna C. Bendell et al.   CANCER

First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014

(2015) B. Basu et al.   CLINICAL CANCER RESEARCH

A Phase I/II Study of the mTOR Inhibitor Everolimus in Combination with HyperCVAD Chemotherapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia

(2015) N. Daver et al.   CLINICAL CANCER RESEARCH

CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization

(2015) D. S. Mortensen et al.   MOLECULAR CANCER THERAPEUTICS

SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1

(2015) Manuele Rebsamen et al.   NATURE

Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1

(2015) S. Wang et al.   SCIENCE

MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies

(2015) G S Choudhary et al.   Cell Death & Disease

PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex

(2015) P. Liu et al.   Cancer Discovery

mTOR inhibitor efficacy is determined by the eIF4E/4E-BP ratio

(2015) Tommy Alain et al.   Oncotarget

Synergistic induction of apoptosis by combination of BTK and dual mTORC1/2 inhibitors in diffuse large B cell lymphoma

(2015) Scott A. Ezell et al.   Oncotarget

Activity of the novel mTOR inhibitor Torin-2 in B-precursor acute lymphoblastic leukemia and its therapeutic potential to prevent Akt reactivation

(2015) Carolina Simioni et al.   Oncotarget

mTOR kinase inhibitors synergize with histone deacetylase inhibitors to kill B-cell acute lymphoblastic leukemia cells

(2015) Brandon R. Beagle et al.   Oncotarget

Rapamycin: One Drug, Many Effects

(2014) Jing Li et al.   Cell Metabolism

PI3K/mTOR Inhibition Markedly Potentiates HDAC Inhibitor Activity in NHL Cells through BIM- and MCL-1-Dependent Mechanisms In Vitro and In Vivo

(2014) M. Rahmani et al.   CLINICAL CANCER RESEARCH

Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels

(2014) A. M. Gomes et al.   HAEMATOLOGICA

Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial

(2014) Fabrice André et al.   LANCET ONCOLOGY

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

Abstract A275: Co-targeting PIM and PI3K/mTOR pathways with a single molecule: Novel orally available combined PIM/PI3K and PIM/PI3K/mTOR kinase inhibitors.

(2014) C. Blanco Aparicio et al.   MOLECULAR CANCER THERAPEUTICS

Abstract C252: A phase 1, dose-escalation study of MLN0128, an investigational oral mammalian target of rapamycin complex 1/2 (mTORC1/2) catalytic inhibitor, in patients (pts) with advanced non-hematologic malignancies.

(2014) J. R. Infante et al.   MOLECULAR CANCER THERAPEUTICS

Resistance to mTOR Kinase Inhibitors in Lymphoma Cells Lacking 4EBP1

(2014) Sharmila Mallya et al.   PLoS One

High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell–like diffuse large B-cell lymphoma cells

(2014) Lesley A. Mathews Griner et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The effect of Bortezomib and Rapamycin on Telomerase Activity in Mantle Cell Lymphoma

(2014) Orit Uziel et al.   Translational Oncology

A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity

(2014) B. C. Grabiner et al.   Cancer Discovery

Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014

(2013) Kurt G. Pike et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Regulation of STAT signaling by acetylation

(2013) Shougang Zhuang   CELLULAR SIGNALLING

Phase I Study of Panobinostat plus Everolimus in Patients with Relapsed or Refractory Lymphoma

(2013) Y. Oki et al.   CLINICAL CANCER RESEARCH

Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial

(2013) John J Bissler et al.   LANCET

Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential

(2013) L M Neri et al.   LEUKEMIA

Dual PI3K/AKT/mTOR Inhibitor BEZ235 Synergistically Enhances the Activity of JAK2 Inhibitor against Cultured and Primary Human Myeloproliferative Neoplasm Cells

(2013) W. Fiskus et al.   MOLECULAR CANCER THERAPEUTICS

BID Preferentially Activates BAK while BIM Preferentially Activates BAX, Affecting Chemotherapy Response

(2013) Kristopher A. Sarosiek et al.   MOLECULAR CELL

mTOR kinase structure, mechanism and regulation

(2013) Haijuan Yang et al.   NATURE

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

(2013) Andrew J Souers et al.   NATURE MEDICINE

Tailoring mTOR-based therapy: molecular evidence and clinical challenges

(2013) Gaetano Santulli et al.   PHARMACOGENOMICS

mTOR Inhibitors Alone and in Combination with JAK2 Inhibitors Effectively Inhibit Cells of Myeloproliferative Neoplasms

(2013) Costanza Bogani et al.   PLoS One

Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

(2013) Karolina Nemes et al.   PLoS One

mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin

(2013) S. A. Kang et al.   SCIENCE

Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation

(2012) N. Gokbuget et al.   BLOOD

Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia

(2012) S. K. Tasian et al.   BLOOD

Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia

(2012) S. L. Maude et al.   BLOOD

Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia

(2012) Kathryn G. Roberts et al.   CANCER CELL

Dual Inhibition of Bcl-2 and Bcl-xL Strikingly Enhances PI3K Inhibition-Induced Apoptosis in Human Myeloid Leukemia Cells through a GSK3- and Bim-Dependent Mechanism

(2012) M. Rahmani et al.   CANCER RESEARCH

mTOR Signaling in Growth Control and Disease

(2012) Mathieu Laplante et al.   CELL

Akt Inhibitors MK-2206 and Nelfinavir Overcome mTOR Inhibitor Resistance in Diffuse Large B-cell Lymphoma

(2012) A. M. Petrich et al.   CLINICAL CANCER RESEARCH

The Clinical Effect of the Dual-Targeting Strategy Involving PI3K/AKT/mTOR and RAS/MEK/ERK Pathways in Patients with Advanced Cancer

(2012) T. Shimizu et al.   CLINICAL CANCER RESEARCH

Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer

(2012) C. M. Rudin et al.   CLINICAL CANCER RESEARCH

Dual mTORC1/2 and HER2 Blockade Results in Antitumor Activity in Preclinical Models of Breast Cancer Resistant to Anti-HER2 Therapy

(2012) C. Garcia-Garcia et al.   CLINICAL CANCER RESEARCH

Efficacy and toxicity of two schedules of bortezomib in patients with recurrent or refractory follicular lymphoma: A randomised phase II trial from the Groupe d’Etude des Lymphomes de l’Adulte (GELA)

(2012) Vincent Ribrag et al.   EUROPEAN JOURNAL OF CANCER

Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma

(2012) J. A. Barnes et al.   HAEMATOLOGICA

Efficacy of the investigational mTOR kinase inhibitor MLN0128/INK128 in models of B-cell acute lymphoblastic leukemia

(2012) M R Janes et al.   LEUKEMIA

Abstract B148: INK128 is a potent and selective TORC1/2 inhibitor with broad oral antitumor activity

(2012) K. Jessen et al.   MOLECULAR CANCER THERAPEUTICS

Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma-dependent apoptosis in lymphoid malignancies

(2011) M. Gupta et al.   BLOOD

Akt-Dependent Glucose Metabolism Promotes Mcl-1 Synthesis to Maintain Cell Survival and Resistance to Bcl-2 Inhibition

(2011) J. L. Coloff et al.   CANCER RESEARCH

Inhibition of mTOR Kinase by AZD8055 Can Antagonize Chemotherapy-induced Cell Death through Autophagy Induction and Down-regulation of p62/Sequestosome 1

(2011) Shengbing Huang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma

(2011) Jonathan H. Schatz et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study

(2011) Stephen M Ansell et al.   LANCET ONCOLOGY

Involvement of the Syk–mTOR pathway in follicular lymphoma cell invasion and angiogenesis

(2011) S Fruchon et al.   LEUKEMIA

CREBBP mutations in relapsed acute lymphoblastic leukaemia

(2011) Charles G. Mullighan et al.   NATURE

Inactivating mutations of acetyltransferase genes in B-cell lymphoma

(2011) Laura Pasqualucci et al.   NATURE

Activation of Akt is associated with poor prognosis and chemotherapeutic resistance in pediatric B-precursor acute lymphoblastic leukemia

(2011) Naoto Morishita et al.   PEDIATRIC BLOOD & CANCER

Simultaneous Inhibition of mTOR-Containing Complex 1 (mTORC1) and MNK Induces Apoptosis of Cutaneous T-Cell Lymphoma (CTCL) Cells

(2011) Michal Marzec et al.   PLoS One

mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling

(2011) V. S. Rodrik-Outmezguine et al.   Cancer Discovery

Proteasome inhibitors in cancer therapy

(2011) Lisa J. Crawford et al.   Journal of Cell Communication and Signaling

MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF- B-dependent lymphoma

(2010) M. A. Milhollen et al.   BLOOD

High immunohistochemical expression of p-AKT predicts inferior survival in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

(2010) Sverker Hasselblom et al.   BRITISH JOURNAL OF HAEMATOLOGY

Genetic Dissection of the Oncogenic mTOR Pathway Reveals Druggable Addiction to Translational Control via 4EBP-eIF4E

(2010) Andrew C. Hsieh et al.   CANCER CELL

Time to Treatment Response in Patients with Follicular Lymphoma Treated with Bortezomib Is Longer Compared with Other Histologic Subtypes

(2010) O. A. O'Connor et al.   CLINICAL CANCER RESEARCH

Phase I study of the oral mammalian target of rapamycin inhibitor everolimus (RAD001) in Japanese patients with relapsed or refractory non-Hodgkin lymphoma

(2010) Kensei Tobinai et al.   INTERNATIONAL JOURNAL OF HEMATOLOGY

Temsirolimus Has Activity in Non–Mantle Cell Non-Hodgkin's Lymphoma Subtypes: The University of Chicago Phase II Consortium

(2010) Sonali M. Smith et al.   JOURNAL OF CLINICAL ONCOLOGY

Bortezomib Plus CHOP-Rituximab for Previously Untreated Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma

(2010) Jia Ruan et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma

(2010) T E Witzig et al.   LEUKEMIA

Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma

(2010) R. Eric Davis et al.   NATURE

Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor

(2010) Matthew R Janes et al.   NATURE MEDICINE

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

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

Everolimus: A Proliferation Signal Inhibitor with Clinical Applications in Organ Transplantation, Oncology, and Cardiology

(2010) Steven Gabardi et al.   PHARMACOTHERAPY

mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs

(2010) R. J. O. Dowling et al.   SCIENCE

Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

(2009) Juan M. García-Martínez et al.   BIOCHEMICAL JOURNAL

A proliferation-inducing ligand mediates follicular lymphoma B-cell proliferation and cyclin D1 expression through phosphatidylinositol 3-kinase-regulated mammalian target of rapamycin activation

(2009) M. Gupta et al.   BLOOD

Results of a phase 2 study of bortezomib in patients with relapsed or refractory indolent lymphoma

(2009) N. Di Bella et al.   BLOOD

Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2

(2009) M. Gupta et al.   BLOOD

Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma

(2009) K. Dunleavy et al.   BLOOD

Potentiating effects of RAD001 (Everolimus) on vincristine therapy in childhood acute lymphoblastic leukemia

(2009) R. Crazzolara et al.   BLOOD

Phosphatidylinositol 3'-Kinase Catalytic Subunit   Gene Amplification Contributes to the Pathogenesis of Mantle Cell Lymphoma

(2009) A. Psyrri et al.   CLINICAL CANCER RESEARCH

The Double-Edged Sword of Autophagy Modulation in Cancer

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

An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1

(2009) Carson C. Thoreen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

(2009) Georg Hess et al.   JOURNAL OF CLINICAL ONCOLOGY

Tor Directly Controls the Atg1 Kinase Complex To Regulate Autophagy

(2009) Y. Kamada et al.   MOLECULAR AND CELLULAR BIOLOGY

An Atg1/Atg13 Complex with Multiple Roles in TOR-mediated Autophagy Regulation

(2009) Yu-Yun Chang et al.   MOLECULAR BIOLOGY OF THE CELL

Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2

(2009) Morris E Feldman et al.   PLOS BIOLOGY

Distinct functional significance of Akt and mTOR constitutive activation in mantle cell lymphoma

(2008) J. Dal Col et al.   BLOOD

mTOR inhibitors are synergistic with methotrexate: an effective combination to treat acute lymphoblastic leukemia

(2008) D. T. Teachey et al.   BLOOD

Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma

(2008) Stephen M. Ansell et al.   CANCER

Outcome of adults with acute lymphocytic leukemia after second salvage therapy

(2008) Susan O'Brien et al.   CANCER

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

Temsirolimus, an Inhibitor of Mammalian Target of Rapamycin

(2008) B. I. Rini   CLINICAL CANCER RESEARCH

Mutations of the PIK3CA Gene in Diffuse Large B Cell Lymphoma

(2008) Yu Baohua et al.   DIAGNOSTIC MOLECULAR PATHOLOGY

Mechanisms of proteasome inhibitor action and resistance in cancer

(2008) David J. McConkey et al.   DRUG RESISTANCE UPDATES

Temsirolimus downregulates p21 without altering cyclin D1 expression and induces autophagy and synergizes with vorinostat in mantle cell lymphoma

(2008) Victor Y. Yazbeck et al.   EXPERIMENTAL HEMATOLOGY

Deforolimus (AP23573) a novel mTOR inhibitor in clinical development

(2008) Monica Mita et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells

(2008) Michael G. Kharas et al.   JOURNAL OF CLINICAL INVESTIGATION

ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo

(2008) Scott Ackler et al.   MOLECULAR CANCER THERAPEUTICS

Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis

(2008) John J. Bissler et al.   NEW ENGLAND JOURNAL OF MEDICINE

Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation

(2008) A. Y. Choo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA