• allosteric
• inhibition
• intrabody
• mTOR
• spatial

• TOR Serine-Threonine Kinases/metabolism
• TOR Serine-Threonine Kinases/chemistry
• TOR Serine-Threonine Kinases/immunology
• Signal Transduction
• Humans
• Mechanistic Target of Rapamycin Complex 1/metabolism
• Protein Conformation
• Sirolimus
• Binding Sites
• Crystallography, X-Ray
• Epitopes
• Tacrolimus Binding Protein 1A/metabolism

• GM117372 NIH GM
• GM144292 T32

• Chemotherapy
• GSDME
• Pyroptosis
• Side effect
• mTOR signaling

• 4E-BP1
• Drug resistance
• Prostate cancer
• TPD52
• c-Myc
• mTOR inhibitor

• Humans
• PTEN Phosphohydrolase/metabolism
• Proto-Oncogene Proteins c-myc/metabolism
• Adaptor Proteins, Signal Transducing/metabolism
• Drug Resistance, Neoplasm
• Cell Line, Tumor
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/drug therapy
• Prostatic Neoplasms/pathology
• TOR Serine-Threonine Kinases/antagonists & inhibitors
• TOR Serine-Threonine Kinases/metabolism
• Male
• Cell Cycle Proteins
• MTOR Inhibitors/pharmacology
• Phosphoproteins/metabolism
• Everolimus/pharmacology
• Androgens/metabolism
• Cell Proliferation/drug effects

• cancer therapy
• mtor signaling
• mtor inhibitors
• drug resistance

• Department of Biotechnology, Ministry of Science and Technology, India
• Indian Council of Medical Research
• Department of Science and Technology, Ministry of Science and Technology, India

• anti‐angiogenesis
• carrier‐free nanoparticles
• immunogenic cell death
• mTOR inhibition
• photodynamic therapy
• synergistic effect

• Photochemotherapy/methods
• Female
• Animals
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Breast Neoplasms/therapy
• TOR Serine-Threonine Kinases/antagonists & inhibitors
• TOR Serine-Threonine Kinases/metabolism
• Humans
• Immunotherapy/methods
• Nanoparticles/chemistry
• Mice
• Cell Line, Tumor
• Photosensitizing Agents/chemistry
• Photosensitizing Agents/pharmacology
• Photosensitizing Agents/therapeutic use
• Mice, Inbred BALB C
• Tumor Microenvironment/drug effects
• Verteporfin/pharmacology
• Verteporfin/chemistry
• Apoptosis/drug effects

• 82222903 National Natural Science Foundation of China
• National Natural Science Foundation of China

• Akt
• Urdamycin
• apoptosis
• cervical cancer
• mTOR
• p53

• Casein kinase 1α
• D4476
• Merkel cell polyomavirus
• Skp1-cullin 1-F-box complex
• TORKinib
• large T
• persistent infection
• phosphorylation
• β-TrCP

• Merkel cell polyomavirus/genetics
• Merkel cell polyomavirus/metabolism
• Humans
• Phosphorylation
• Casein Kinase Ialpha/metabolism
• Casein Kinase Ialpha/genetics
• beta-Transducin Repeat-Containing Proteins/metabolism
• beta-Transducin Repeat-Containing Proteins/genetics
• Antigens, Viral, Tumor/metabolism
• Antigens, Viral, Tumor/genetics
• Host-Pathogen Interactions
• Proteolysis
• Virus Replication
• Protein Binding
• Antigens, Polyomavirus Transforming/metabolism
• Antigens, Polyomavirus Transforming/genetics
• Polyomavirus Infections/virology
• Polyomavirus Infections/metabolism
• Polyomavirus Infections/genetics

• SAP# 4100083097 Pennsylvania Department of Health (PA DOH)

• Bioluminescence resonance energy transfer (BRET)
• Kinase inhibitors
• Molecular docking
• Protein kinase

• Humans
• MAP Kinase Kinase 3
• Pyrimidines/chemistry
• Structure-Activity Relationship
• Phosphorylation
• Cell Proliferation
• Neoplasms
• Protein Kinase Inhibitors/chemistry

• Ku-0063794
• atherogenic diet
• lipotoxicity
• mTOR
• mouse
• non-alcoholic steatohepatitis

• Thailand Science Research and Innovation
• Office of National Higher Education Science Research and Innovation Policy Council

• Anti-proliferative
• MLN0128
• NO donor
• Structure-activity relationship
• mTOR inhibitors

• Apoptosis
• Pathological angiogenesis
• Rapamycin and rapalogues
• Signalling cascade
• mTOR

• Humans
• Sirolimus
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• TOR Serine-Threonine Kinases/metabolism
• Neoplasms/metabolism
• Carcinogenesis
• Cell Transformation, Neoplastic
• Cell Proliferation

• BCAA catabolism
• BCKDK
• NSCLC
• Rab1A
• mTORC1

• Kleiber’s law
• Xenopus
• cell size
• energy budget
• metabolism
• oxygen consumption rate
• polyploidy
• scaling

• Animals
• Triploidy
• Xenopus laevis/genetics
• Polyploidy
• Ploidies
• Diploidy
• Cell Membrane

• R35 GM118183 NIGMS NIH HHS

• ATP internalization
• EMT
• Invasion
• Macropinocytosis
• Purinergic receptor
• Tumor microenvironment

• lung cancer
• mTOR
• mTOR inhibitors
• rapalogs
• tetrahydroquinoline

Tuberous sclerosis complex (TSC) is a rare genetic disease of autosomal dominant transmission that, in most cases, results from the presence of pathogenic variants of the TSC1 or TSC2 genes, encoding hamartin and tuberin, respectively. It is a multisystemic disease, affecting most frequently the brain, skin, kidney, and heart. The wide variety of possible clinical manifestations, given this multisystem dimension, makes the follow-up of patients with TSC an exercise of multidisciplinarity. In fact, these patients may require the intervention of various medical specialties, which thus have to combine their efforts to practice a medicine that is truly holistic. The past few years have witnessed a dramatic leap not only in the diagnosis and management of TSC patients, with standard monitoring recommendations, but also in the therapeutic field, with the use of mTORC1 inhibitors. In this article, we review the clinical manifestations associated with TSC, as well as the treatment and follow-up strategies that should be implemented, from a multidisciplinary perspective.

• care management
• multidisciplinary communications
• patient
• tuberous sclerosis complex

• STK11 (LKB1)
• metabolism
• non-small cell lung cancer
• personalized medicine
• target

Glioblastoma is a type of brain cancer with aggressive and invasive nature. Such features result from increased proliferation and migration and also poor apoptosis of glioma cells leading to resistance to current treatments such as chemotherapy and radiotherapy. In recent studies, micro RNAs have been introduced as a novel target for treating glioblastoma via regulation of apoptotic signaling pathway, remarkably PI3K/AKT, which affect cellular functions and blockage or progression of the tumor. In this review, we focus on PI3K/AKT signaling pathway and other related apoptotic processes contributing to glioblastoma and investigate the role of micro RNAs interfering in apoptosis, invasion and proliferation of glioma through such apoptotic processes pathways. Databases NCBI, PubMed, and Web of Science were searched for published English articles using keywords such as 'miRNA OR microRNA', 'Glioblastoma', 'apoptotic pathways', 'PI3K and AKT', 'Caspase signaling Pathway' and 'Notch pathway'. Most articles were published from 7 May 2015 to 16 June 2020. This study focused on PI3K/AKT signaling pathway affecting glioma cells in separated subparts. Also, other related apoptotic pathways as the Caspase cycle and Notch have been also investigated. Nearly 40 miRNAs were found as tumor suppressors or onco-miRNA, and their targets, which regulated subcomponents participating in proliferation, invasion, and apoptosis of the tumoral cells. Our review reveals that miRNAs affect key molecules in signaling apoptotic pathways, partly PI3K/AKT, making them potential therapeutic targets to overcome the tumor. However, their utility as a novel treatment for glioblastoma requires further examination and investigation.

• Glioblastoma
• Micro RNA
• PI3K/AKT pathway

• CRISPR-Cas9 screen
• cancer
• chemoresistance
• inhibitor of mitochondrial transcription
• mtDNA

• CRISPR-Cas Systems
• DNA, Mitochondrial/genetics
• Down-Regulation
• Gene Editing
• Mitochondria/genetics
• Mitochondria/metabolism
• Transcription, Genetic

• Vetenskapsrådet (VR)
• Cancerfonden (Swedish Cancer Society)
• Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
• EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC)
• Novo Nordisk Fonden (NNF)
• Diabetesfonden (Stiftelsen Svenska Diabetesförbundets Forskningsfond)

This article reviews current treatment practices for thyroid cancer with a focus on novel targeted molecular therapy. Rapidly expanding knowledge of the molecular biology of these cancers coupled with the increased availability of genetic testing has led to exciting paradigm shifts in treatment strategies for these tumor types. We aim to provide up-to-date information on these state-of-the-art therapies as a guide for clinicians who specialize in the treatments of thyroid cancer.

Thyroid cancer is the most common type of endocrine malignancy comprising 2–3% of all cancers, with a constant rise in the incidence rate. The standard first-line treatments for thyroid cancer include surgery and radioactive iodine ablation, and a majority of patients show a good response to these therapies. Despite a better response and outcome, approximately twenty percent of patients develop disease recurrence and distant metastasis. With improved knowledge of molecular dysregulation and biological characteristics of thyroid cancer, the development of new treatment strategies comprising novel targets has accelerated. Biomarker-driven targeted therapies have now emerged as a trend for personalized treatments in patients with advanced cancers, and several multiple receptor kinase inhibitors have entered clinical trials (phase I/II/III) to evaluate their safety and efficacy. Most extensively investigated and clinically approved targeted therapies in thyroid cancer include the tyrosine receptor kinase inhibitors that target antiangiogenic markers, BRAF mutation, PI3K/AKT, and MAPK pathway components. In this review, we focus on the current advances in targeted mono- and combination therapies for various types of thyroid cancer.

• biomarker
• targeted therapy
• thyroid cancer
• tyrosine-kinase inhibitors

• 4EBP1, eIF4E-binding protein 1
• Baf, bafilomycin A1
• CETSA, cellular thermal shift assay
• CHX, cycloheximide
• CQ, chloroquine
• IB, immunoblotting
• ICB, immune checkpoint blockade
• IHC, immunohistochemistry
• Immune checkpoint blockade
• LLC, Lewis lung carcinoma
• Lysosome
• MDSCs, myeloid-derived suppressor cells
• NAG, β-N-acetylglucosaminidase
• NSCLC, non-small cell lung cancer
• PD-1, programmed cell death-1
• PD-L1
• PD-L1, programmed cell death ligand- 1
• SPR, surface plasmon resonance
• TBM-1, tubeimoside-1
• TFEB, nuclear transcriptional factor EB
• TILs, tumor-infiltrating lymphocytes
• Transcription factor EB
• Tregs, regulatory T-lymphocytes
• mTOR
• mTOR, mammalian target of rapamycin
• p70S6K, phosphorylation of p70 S6 kinase
• qRT-PCR, quantitative real-time polymerase chain reaction

• Gαi1
• cell migration
• cell proliferation
• renal cell carcinoma
• therapeutic targets

• E3 ubiquitin ligase
• GSK3
• PD-L1
• cancer therapy
• mTOR
• protein degradation
• resistance

• Glycogen Synthase Kinase 3
• Mechanistic Target of Rapamycin Complex 2
• Neoplasms/drug therapy
• Phosphatidylinositol 3-Kinases
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

• cartilage-forming malignancy
• chondrosarcoma
• mesenchymal stem cell
• primary bone tumor

• Cancer
• PD-L1
• Rapalogs
• mTOR
• mTORC1
• p70S6K

Sesamin, the major furofuran lignan found in the seeds of Sesamum indicum L., has been investigated for its various medicinal properties. In the present study, the anti-leukemic effects of sesamin and its underlying mechanisms were investigated in MOLT-4 and NB4 acute leukemic cells. Leukemic cells were treated with various concentrations of sesamin. Cell viability was determined using an MTT assay. Flow cytometry using Annexin V-FITC/PI staining and anti-LC3/FITC antibodies was applied to detect the level of apoptosis and autophagy, respectively. Reverse transcription-quantitative PCR was performed to examine the alterations in the mRNA expression of apoptotic and autophagic genes. In addition, bioinformatics tools were used to predict the possible interactions between sesamin and its targets. The results revealed that sesamin inhibited MOLT-4 and NB4 cell proliferation in a dose-dependent manner. In addition, sesamin induced both apoptosis and autophagy. In sesamin-treated cells, the gene expression levels of caspase 3 and unc-51 like autophagy activating kinase 1 (ULK1) were upregulated, while those of mTOR were downregulated compared with in the control. Notably, the protein-chemical interaction network indicated that caspase 3, mTOR and ULK1 were the essential factors involved in the effects of sesamin treatment, as with anticancer agents, such as rapamycin, AZD8055, Torin1 and 2. Overall, the findings of the present study suggested that sesamin inhibited MOLT-4 and NB4 cell proliferation, and induced apoptosis and autophagy through the regulation of caspase 3 and mTOR/ULK1 signaling, respectively.

• apoptosis
• autophagy
• leukemia
• protein-chemical interaction
• sesamin

• PI3K
• PTEN
• prostate cancer
• targeted therapy

• Animals
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Biomarkers, Tumor
• DNA Damage/drug effects
• Disease Management
• Disease Susceptibility
• Gene Expression Regulation, Neoplastic
• Humans
• Immunomodulation/drug effects
• Male
• Molecular Targeted Therapy
• PTEN Phosphohydrolase/genetics
• PTEN Phosphohydrolase/metabolism
• Prognosis
• Prostatic Neoplasms/diagnosis
• Prostatic Neoplasms/etiology
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/therapy
• Signal Transduction/drug effects
• Treatment Outcome

• 27894 Cancer Research UK
• A27894 Cancer Research UK

Idiopathic pulmonary fibrosis (IPF) is characterised by the progressive deposition of excessive extracellular matrix proteins within the lung parenchyma and represents the most rapidly progressive and fatal of all fibrotic conditions. Current anti-fibrotic drugs approved for the treatment of IPF fail to halt disease progression and have significant side-effect profiles. Therefore, there remains a pressing need to develop novel therapeutic strategies for IPF. Mammalian target of rapamycin (mTOR) forms the catalytic subunit of two complexes, mTORC1 and mTORC2. mTORC1 acts as critical cellular sensor which integrates intracellular and extracellular signals to reciprocally regulate a variety of anabolic and catabolic processes. The emerging evidence for a critical role for mTORC1 in influencing extracellular matrix production, metabolism, autophagy and senescence in the setting of IPF highlights this axis as a novel therapeutic target with the potential to impact multiple IPF pathomechanisms.

Current evidence supports the scientific rationale for targeting the mTOR pathway in idiopathic pulmonary fibrosishttps://bit.ly/33OQiYf

• AKT-mTORC1
• Myc
• lncRNA EPIC1
• rapamycin resistance

• fetal development
• intrauterine growth restriction
• mTOR signaling
• macrosomia
• placenta

• Rapalink-1
• mTOR inhibitor
• renal cell carcinoma
• sunitinib resistance
• temsirolimus

The mechanistic target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation and survival in response to the availability of energy sources and growth factors. Cancer development and progression is often associated with constitutive activation of the mTOR pathway, thus justifying mTOR inhibition as a promising approach to cancer treatment and prevention. However, development of previous rapamycin analogues has been complicated by their induction of adverse side effects and variable efficacy. Since mTOR pathway regulation involves multiple feedback mechanisms that may be differentially activated depending on the degree of mTOR inhibition, we investigated whether rapamycin dosing could be adjusted to achieve chemopreventive efficacy without side effects. Thus, we tested the efficacy of two doses of a novel, highly bioavailable nanoformulation of rapamycin, Rapatar, in a mouse prostate cancer model (male mice with prostate epithelium-specific Pten-knockout). We found that the highest efficacy was achieved by the lowest dose of Rapatar used in the study. While both doses tested were equally effective in suppressing proliferation of prostate epithelial cells, higher dose resulted in activation of feedback circuits that reduced the drug’s tumor preventive efficacy. These results demonstrate that low doses of highly bioavailable mTOR inhibitor, Rapatar, may provide safe and effective cancer prevention.

• PTEN
• mTOR
• prevention
• prostate cancer
• rapamycin

Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer that has not been well characterized. It accounts for less than 10% of all endometrial cancers and 80% of endometrial cancer–related deaths. Currently, staging surgery together with chemotherapy or radiotherapy, especially vaginal cuff brachytherapy, is the main treatment strategy for USC. Whole-exome sequencing combined with preclinical and clinical studies are verifying a series of effective and clinically accessible inhibitors targeting frequently altered genes, such as HER2 and PI3K3CA, in varying USC patient populations. Some progress has also been made in the immunotherapy field. The PD-1/PD-L1 pathway has been found to be activated in many USC patients, and clinical trials of PD-1 inhibitors in USC are underway. This review updates the progress of research regarding the molecular pathogenesis and putative clinical management of USC.

• endometrial cancer
• uterine serous carcinoma

• PFK15
• PFKFB3
• TSC
• mTORC1
• rapamycin

• Animals
• Cell Line
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Fibroblasts/cytology
• Fibroblasts/drug effects
• Fibroblasts/metabolism
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Heterografts
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors
• Mechanistic Target of Rapamycin Complex 1/genetics
• Mechanistic Target of Rapamycin Complex 1/metabolism
• Mice
• Phosphofructokinase-2/genetics
• Phosphofructokinase-2/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA, Small Interfering/genetics
• RNA, Small Interfering/metabolism
• Rapamycin-Insensitive Companion of mTOR Protein/antagonists & inhibitors
• Rapamycin-Insensitive Companion of mTOR Protein/genetics
• Rapamycin-Insensitive Companion of mTOR Protein/metabolism
• Rats
• Regulatory-Associated Protein of mTOR/antagonists & inhibitors
• Regulatory-Associated Protein of mTOR/genetics
• Regulatory-Associated Protein of mTOR/metabolism
• Signal Transduction
• Sirolimus/pharmacology
• Tuberous Sclerosis/genetics
• Tuberous Sclerosis/metabolism
• Tuberous Sclerosis/pathology
• Tuberous Sclerosis Complex 1 Protein/deficiency
• Tuberous Sclerosis Complex 1 Protein/genetics
• Tuberous Sclerosis Complex 2 Protein/deficiency
• Tuberous Sclerosis Complex 2 Protein/genetics

The goal of many single-cell studies on eukaryotic cells is to gain insight into the biochemical reactions that control cell fate and state. In this paper we introduce the concept of Effective Stoichiometric Spaces (ESS) to guide the reconstruction of biochemical networks from multiplexed, fixed time-point, single-cell data. In contrast to methods based solely on statistical models of data, the ESS method leverages the power of the geometric theory of toric varieties to begin unraveling the structure of chemical reaction networks (CRN). This application of toric theory enables a data-driven mapping of covariance relationships in single-cell measurements into stoichiometric information, one in which each cell subpopulation has its associated ESS interpreted in terms of CRN theory. In the development of ESS we reframe certain aspects of the theory of CRN to better match data analysis. As an application of our approach we process cytomery- and image-based single-cell datasets and identify differences in cells treated with kinase inhibitors. Our approach is directly applicable to data acquired using readily accessible experimental methods such as Fluorescence Activated Cell Sorting (FACS) and multiplex immunofluorescence.

We introduce a new notion, which we call the effective stoichiometric space (ESS), that elucidates network structure from the covariances of single-cell multiplex data. The ESS approach differs from methods that are based on purely statistical models of data: it allows a completely new and data-driven translation of the theory of toric varieties in geometry and specifically their role in chemical reaction networks (CRN). In the process, we reframe certain aspects of the theory of CRN. As illustrations of our approach, we find stoichiometry in different single-cell datasets, and pinpoint dose-dependence of network perturbations in drug-treated cells.

• Acanthamoeba
• Balamuthia
• CNS infection
• Drug screening
• Naegleria
• ReFRAME library

• Acanthamoeba/drug effects
• Amebiasis/drug therapy
• Amebiasis/parasitology
• Amoebozoa/drug effects
• Antiprotozoal Agents/pharmacology
• Carbazoles/pharmacology
• Carbazoles/therapeutic use
• Cell Culture Techniques
• Central Nervous System Protozoal Infections/drug therapy
• Central Nervous System Protozoal Infections/parasitology
• Culture Media
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Enzyme Inhibitors/pharmacology
• Enzyme Inhibitors/therapeutic use
• Furans
• Heterocyclic Compounds, 4 or More Rings/pharmacology
• Heterocyclic Compounds, 4 or More Rings/therapeutic use
• Inhibitory Concentration 50
• Naegleria/drug effects
• Oxazines/pharmacology
• Oxazines/therapeutic use
• Panobinostat/pharmacology
• Panobinostat/therapeutic use
• Plicamycin/pharmacology
• Plicamycin/therapeutic use
• Pyrimidines/pharmacology
• Pyrimidines/therapeutic use

• KL2 TR001444 NCATS NIH HHS
• R21 AI123594 NIAID NIH HHS
• R21 AI133394 NIAID NIH HHS
• R21 AI142487 NIAID NIH HHS

• Cell Line, Tumor
• Drug Resistance, Neoplasm/drug effects
• Female
• Gastrointestinal Stromal Tumors/drug therapy
• Gastrointestinal Stromal Tumors/genetics
• Gene Regulatory Networks/drug effects
• Genetic Heterogeneity
• High-Throughput Nucleotide Sequencing/methods
• Humans
• Mutation
• Protein Kinase Inhibitors/pharmacology
• Proto-Oncogene Proteins c-kit/genetics
• Pyrazoles/pharmacology
• Pyrimidines/pharmacology
• Salvage Therapy
• Sequence Analysis, DNA
• Signal Transduction

• I01 BX000338 BLRD VA
• I01 BX005358 BLRD VA

• Activating Transcription Factor 4/genetics
• Activating Transcription Factor 4/metabolism
• Biosynthetic Pathways/drug effects
• Biosynthetic Pathways/genetics
• Cell Differentiation/drug effects
• Cell Differentiation/genetics
• Cells, Cultured
• Collagen/biosynthesis
• Extracellular Matrix/metabolism
• Fibroblasts/cytology
• Fibroblasts/drug effects
• Fibroblasts/metabolism
• Gene Expression Regulation/drug effects
• Glycine/biosynthesis
• Humans
• Mechanistic Target of Rapamycin Complex 1/genetics
• Mechanistic Target of Rapamycin Complex 1/metabolism
• Myofibroblasts/cytology
• Myofibroblasts/drug effects
• Myofibroblasts/metabolism
• Serine/biosynthesis
• Signal Transduction/drug effects
• Transforming Growth Factor beta1/pharmacology

• MC_UP_1202/1 Medical Research Council
• FC001033 Cancer Research UK
• FC001033 Medical Research Council
• FC001033 Arthritis Research UK
• FC001033 Wellcome Trust
• MR/K024078/1 Medical Research Council
• BB/P504440/1 Biotechnology and Biological Sciences Research Council
• Wellcome Trust
• BB/M502844/1 Biotechnology and Biological Sciences Research Council

Multidrug resistance (MDR) is a major reason for the failure of acute myeloid leukemia (AML) therapy. Agents that reverse MDR and sensitize AML cells to chemotherapy are of great clinical significance. The present study developed Adriamycin (Adr)-resistant cell lines, namely K562/Adr200 and K562/Adr500, which exhibited MDR. The upregulation of ATP-binding cassette subfamily B member 1 (ABCB1) was confirmed as the mechanism of resistance by reverse transcription-quantitative polymerase chain reaction and western blot analyses. Subsequently, the role of the mammalian target of rapamycin (mTOR) kinase inhibitor, WYE-354, in sensitizing the K562/Adr200 and K562/Adr500 cell lines to Adr was evaluated. At sub-cytotoxic concentrations, WYE-354 increased Adr cytotoxicity in the K562/Adr200 and K562/Adr500 cells. WYE-354 restored Adr sensitivity in the resistant cells by inhibiting ABCB1-mediated substrate efflux, thereby leading to an accumulation of Adr, an increase in Adr-mediated G2/M cell cycle arrest and the induction of apoptosis. Furthermore, WYE-354 stimulated the ATPase activity of ABCB1, which was consistent with in silico predictions using a human ABCB1 mouse homology model, indicating that WYE-354 is a potent substrate of ABCB1. WYE-354 did not regulate the expression of ABCB1 at the concentrations used in the present study. These findings indicate that WYE-354 may be a competitive inhibitor of ABCB1-mediated efflux and a potential candidate in combination with standard chemotherapy for overcoming MDR. Further clinical investigations are warranted to validate this combination in vivo.