PI3K/AKT/mTOR pathway in multiple myeloma: from basic biology to clinical promise

TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenström's macroglobulinemia

(2016) Irene M. Ghobrial et al.   AMERICAN JOURNAL OF HEMATOLOGY

The PI3K/AKT Pathway as a Target for Cancer Treatment

(2016) Ingrid A. Mayer et al.   Annual Review of Medicine

Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes

(2016) K. M. Kortum et al.   BLOOD

Smac mimetic LCL161 overcomes protective ER stress induced by obatoclax, synergistically causing cell death in multiple myeloma

(2016) Vijay Ramakrishnan et al.   Oncotarget

Microenvironment drug resistance in multiple myeloma: emerging new players

(2016) Lucia Di Marzo et al.   Oncotarget

Signaling Pathways and Emerging Therapies in Multiple Myeloma

(2016) Vijay Ramakrishnan et al.   Current Hematologic Malignancy Reports

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

(2015) A. Gunther et al.   HAEMATOLOGICA

MicroRNA-451 regulates stemness of side population cells via PI3K/Akt/mTOR signaling pathway in multiple myeloma

(2015) Juan Du et al.   Oncotarget

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

(2015) A. Gunther et al.   HAEMATOLOGICA

The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma

(2014) A. Spencer et al.   BLOOD

Outcomes in patients with relapsed or refractory multiple myeloma in a phase I study of everolimus in combination with lenalidomide

(2014) Andrew J. Yee et al.   BRITISH JOURNAL OF HAEMATOLOGY

Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy

(2014) Jens G. Lohr et al.   CANCER CELL

Phase I study of the MEK inhibitor trametinib in combination with the AKT inhibitor afuresertib in patients with solid tumors and multiple myeloma

(2014) Anthony W. Tolcher et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Selective and Potent Akt Inhibition Triggers Anti-Myeloma Activities and Enhances Fatal Endoplasmic Reticulum Stress Induced by Proteasome Inhibition

(2014) N. Mimura et al.   CANCER RESEARCH

Multiple mechanisms contribute to the synergistic anti-myeloma activity of the pan-histone deacetylase inhibitor LBH589 and the rapalog RAD001

(2014) Vijay Ramakrishnan et al.   LEUKEMIA RESEARCH

Delineating the mTOR Kinase Pathway Using a Dual TORC1/2 Inhibitor, AZD8055, in Multiple Myeloma

(2014) D. Cirstea et al.   MOLECULAR CANCER THERAPEUTICS

TORC1 and class I HDAC inhibitors synergize to suppress mature B cell neoplasms

(2014) John K. Simmons et al.   Molecular Oncology

PI3K and cancer: lessons, challenges and opportunities

(2014) David A. Fruman et al.   NATURE REVIEWS DRUG DISCOVERY

Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120)

(2013) M. V. Dhodapkar et al.   BLOOD

Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients

(2013) S K Kumar et al.   LEUKEMIA

Understanding the interplay between the proteasome pathway and autophagy in response to dual PI3K/mTOR inhibition in myeloma cells is essential for their effective clinical application

(2013) L I Aronson et al.   LEUKEMIA

Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma

(2013) S V Rajkumar et al.   LEUKEMIA

PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1

(2013) H. Ebi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study

(2012) Andrzej J. Jakubowiak et al.   BRITISH JOURNAL OF HAEMATOLOGY

JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer

(2012) Adrian Britschgi et al.   CANCER CELL

SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma

(2012) Vanesa Fernández-Sáiz et al.   NATURE CELL BIOLOGY

Anti-Myeloma Activity of Akt Inhibition Is Linked to the Activation Status of PI3K/Akt and MEK/ERK Pathway

(2012) Vijay Ramakrishnan et al.   PLoS One

Defining the role of TORC1/2 in multiple myeloma

(2011) P. Maiso et al.   BLOOD

AKT Inhibition Relieves Feedback Suppression of Receptor Tyrosine Kinase Expression and Activity

(2011) Sarat Chandarlapaty et al.   CANCER CELL

mTORC1- and mTORC2-interacting proteins keep their multifunctional partners focused

(2011) Ismael Bracho-Valdés et al.   IUBMB LIFE

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

Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study

(2011) Irene M Ghobrial et al.   LANCET ONCOLOGY

MRK003, a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma

(2011) V Ramakrishnan et al.   LEUKEMIA

Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma

(2011) W-J Chng et al.   LEUKEMIA

Initial genome sequencing and analysis of multiple myeloma

(2011) Michael A. Chapman et al.   NATURE

TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells

(2010) Vijay Ramakrishnan et al.   AMERICAN JOURNAL OF HEMATOLOGY

Mutated RAS and constitutively activated Akt delineate distinct oncogenic pathways, which independently contribute to multiple myeloma cell survival

(2010) T. Steinbrunn et al.   BLOOD

Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor

(2010) B. Hoang et al.   BLOOD

ERK1/2 Phosphorylate Raptor to Promote Ras-dependent Activation of mTOR Complex 1 (mTORC1)

(2010) Audrey Carriere et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

NVP-BEZ235, a dual pan class I PI3 kinase and mTOR inhibitor, promotes osteogenic differentiation in human mesenchymal stromal cells

(2010) Sally K Martin et al.   JOURNAL OF BONE AND MINERAL RESEARCH

Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis

(2010) Carmen Palacios et al.   LEUKEMIA RESEARCH

Myeloma cell growth inhibition is augmented by synchronous inhibition of the insulin-like growth factor-1 receptor by NVP-AEW541 and inhibition of mammalian target of rapamycin by Rad001

(2009) Philipp Baumann et al.   ANTI-CANCER DRUGS

Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

(2009) O. Landgren et al.   BLOOD

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

DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival

(2009) Timothy R. Peterson et al.   CELL

Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma

(2009) Sherif S. Farag et al.   LEUKEMIA RESEARCH

Hotspot mutations of PIK3CA and AKT1 genes are absent in multiple myeloma

(2009) Said I. Ismail et al.   LEUKEMIA RESEARCH

Sorafenib, a dual Raf kinase/vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs

(2009) V Ramakrishnan et al.   ONCOGENE

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

Clinical and biological significance of RAS mutations in multiple myeloma

(2008) W J Chng et al.   LEUKEMIA