abstract：:Notch signaling is aberrantly activated in approximately one third of non-small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor, and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14...

journal_title：Molecular cancer therapeutics

authors： Morgan KM,Fischer BS,Lee FY,Shah JJ,Bertino JR,Rosenfeld J,Singh A,Khiabanian H,Pine SR

更新日期：2017-12-01 00:00:00

abstract：:Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selec...

journal_title：Molecular cancer therapeutics

authors： de Oliveira CE,Gasparoto TH,Pinheiro CR,Amôr NG,Nogueira MRS,Kaneno R,Garlet GP,Lara VS,Silva JS,Cavassani KA,Campanelli AP

更新日期：2017-12-01 00:00:00

abstract：:The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of chromosome segregation and is the subject of novel targeted therapy approaches by small-molecule inhibitors. Although the first TTK inhibitors have entered phase I dose escalating studies in combination with taxane chemotherapy, a patient stratifi...

journal_title：Molecular cancer therapeutics

authors： Zaman GJR,de Roos JADM,Libouban MAA,Prinsen MBW,de Man J,Buijsman RC,Uitdehaag JCM

更新日期：2017-11-01 00:00:00

abstract：:Pancreatic ductal adenocarcinoma (PDAC) is one of the most chemotherapy- and radiotherapy-resistant tumors. The c-Met and Hedgehog (Hh) pathways have been shown previously by our group to be key regulatory pathways in the primary tumor growth and metastases formation. Targeting both the HGF/c-Met and Hh pathways has s...

journal_title：Molecular cancer therapeutics

authors： Rucki AA,Xiao Q,Muth S,Chen J,Che X,Kleponis J,Sharma R,Anders RA,Jaffee EM,Zheng L

更新日期：2017-11-01 00:00:00

abstract：:Cationic liposomes have been used for targeted drug delivery to tumor blood vessels, via mechanisms that are not fully elucidated. Doxorubicin (Dox)-loaded liposomes were prepared that incorporate a cationic lipid; 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), along with a small amount of porphyrin-phospholipid (P...

journal_title：Molecular cancer therapeutics

authors： Luo D,Geng J,Li N,Carter KA,Shao S,Atilla-Gokcumen GE,Lovell JF

更新日期：2017-11-01 00:00:00

abstract：:Heat shock protein 90 (Hsp90) is widely overexpressed in cancer cells and necessary for maintenance of malignant phenotypes. Hsp90 inhibition induces tumor cell death through degradation of its client oncoproteins and has shown promises in preclinical studies. However, the mechanism by which Hsp90 inhibitors kill tumo...

journal_title：Molecular cancer therapeutics

authors： Tong J,Tan S,Nikolovska-Coleska Z,Yu J,Zou F,Zhang L

更新日期：2017-09-01 00:00:00

abstract：:Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma, indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084...

journal_title：Molecular cancer therapeutics

authors： Wu CX,Xu A,Zhang CC,Olson P,Chen L,Lee TK,Cheung TT,Lo CM,Wang XQ

更新日期：2017-08-01 00:00:00

abstract：:Inactivation of NF2/Merlin causes the autosomal-dominant cancer predisposition syndrome familial neurofibromatosis type 2 (NF2) and contributes to the development of malignant pleural mesothelioma (MPM). To develop a targeted therapy for NF2-mutant tumors, we have exploited the recent realization that Merlin loss driv...

journal_title：Molecular cancer therapeutics

authors： Cooper J,Xu Q,Zhou L,Pavlovic M,Ojeda V,Moulick K,de Stanchina E,Poirier JT,Zauderer M,Rudin CM,Karajannis MA,Hanemann CO,Giancotti FG

更新日期：2017-08-01 00:00:00

abstract：:The primary mechanism of antibody-drug conjugates (ADC) is targeted delivery of a cytotoxic payload to tumor cells via cancer-associated membrane receptors. However, the tumor microenvironment likely plays a role in ADC penetration, distribution, and processing and thus impacts the overall antitumor activity. Here, we...

journal_title：Molecular cancer therapeutics

authors： Li F,Ulrich M,Jonas M,Stone IJ,Linares G,Zhang X,Westendorf L,Benjamin DR,Law CL

更新日期：2017-07-01 00:00:00

abstract：:The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets but has yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pa...

journal_title：Molecular cancer therapeutics

authors： Ding J,Fishel ML,Reed AM,McAdams E,Czader MB,Cardoso AA,Kelley MR

更新日期：2017-07-01 00:00:00

abstract：:Barasertib (AZD1152), a highly potent and selective aurora kinase B inhibitor, gave promising clinical activity in elderly acute myeloid leukemia (AML) patients. However, clinical utility was limited by the requirement for a 7-day infusion. Here we assessed the potential of a nanoparticle formulation of the selective ...

journal_title：Molecular cancer therapeutics

authors： Floc'h N,Ashton S,Taylor P,Trueman D,Harris E,Odedra R,Maratea K,Derbyshire N,Caddy J,Jacobs VN,Hattersley M,Wen S,Curtis NJ,Pilling JE,Pease EJ,Barry ST

更新日期：2017-06-01 00:00:00

abstract：:The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n = 166), we here provided ...

journal_title：Molecular cancer therapeutics

authors： Ding L,Ren J,Zhang D,Li Y,Huang X,Ji J,Hu Q,Wang H,Ni Y,Hou Y

更新日期：2017-06-01 00:00:00

abstract：:Transforming growth factor (TGF)-β contributes to the malignant phenotype of glioblastoma by promoting invasiveness and angiogenesis and creating an immunosuppressive microenvironment. So far, TGF-β1 and TGF-β2 isoforms have been considered to act in a similar fashion without isoform-specific function in glioblastoma....

journal_title：Molecular cancer therapeutics

authors： Seystahl K,Papachristodoulou A,Burghardt I,Schneider H,Hasenbach K,Janicot M,Roth P,Weller M

更新日期：2017-06-01 00:00:00

abstract：:We previously reported that the EGFR-targeted inhibitor erlotinib induces G1 arrest of squamous cell carcinoma of the head and neck (SCCHN) cell lines without inducing significant apoptosis. Large-scale genomic studies suggest that >50% of SCCHN cases have activation of PI3K pathways. This study investigated whether c...

journal_title：Molecular cancer therapeutics

authors： Anisuzzaman AS,Haque A,Wang D,Rahman MA,Zhang C,Chen Z,Chen ZG,Shin DM,Amin AR

更新日期：2017-04-01 00:00:00

abstract：:Although proteasome inhibitors such as bortezomib had significant therapeutic effects in multiple myeloma and mantel cell lymphoma, they exhibited minimal clinical activity as a monotherapy for solid tumors, including colorectal cancer. We found in this study that proteasome inhibition induced a remarkable nuclear exp...

journal_title：Molecular cancer therapeutics

authors： Wu T,Chen W,Zhong Y,Hou X,Fang S,Liu CY,Wang G,Yu T,Huang YY,Ouyang X,Li HQ,Cui L,Yang Y

更新日期：2017-04-01 00:00:00

abstract：:The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, w...

journal_title：Molecular cancer therapeutics

authors： Kuo YH,Chiang EI,Chao CY,Rodriguez RL,Chou PY,Tsai SY,Pai MH,Tang FY

更新日期：2017-03-01 00:00:00

abstract：:Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained...

journal_title：Molecular cancer therapeutics

authors： Talbert EE,Yang J,Mace TA,Farren MR,Farris AB,Young GS,Elnaggar O,Che Z,Timmers CD,Rajasekera P,Maskarinec JM,Bloomston M,Bekaii-Saab T,Guttridge DC,Lesinski GB

更新日期：2017-02-01 00:00:00

abstract：:RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germline RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1 expression has clinicopathologic significance in sporadic breast canc...

journal_title：Molecular cancer therapeutics

authors： Arora A,Parvathaneni S,Aleskandarany MA,Agarwal D,Ali R,Abdel-Fatah T,Green AR,Ball GR,Rakha EA,Ellis IO,Sharma S,Madhusudan S

更新日期：2017-01-01 00:00:00

abstract：:To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC versus aspirin on three human (A2780, SKOV3ip1, and HeyA8) and a mouse (ID8) ovar...

journal_title：Molecular cancer therapeutics

authors： Huang Y,Lichtenberger LM,Taylor M,Bottsford-Miller JN,Haemmerle M,Wagner MJ,Lyons Y,Pradeep S,Hu W,Previs RA,Hansen JM,Fang D,Dorniak PL,Filant J,Dial EJ,Shen F,Hatakeyama H,Sood AK

更新日期：2016-12-01 00:00:00

abstract：:Endocrine therapy has been highly effective for the treatment of estrogen receptor-positive breast cancer, but endocrine resistance develops in a significant proportion of patients. In an effort to develop novel therapeutic strategies for the treatment of endocrine-resistant breast cancer, we have evaluated a potent a...

journal_title：Molecular cancer therapeutics

authors： Lu J,McEachern D,Li S,Ellis MJ,Wang S

更新日期：2016-12-01 00:00:00

abstract：:Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition...

journal_title：Molecular cancer therapeutics

authors： Yamaoka T,Ohmori T,Ohba M,Arata S,Kishino Y,Murata Y,Kusumoto S,Ishida H,Shirai T,Hirose T,Ohnishi T,Sasaki Y

更新日期：2016-12-01 00:00:00

abstract：:The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables ac...

journal_title：Molecular cancer therapeutics

authors： Delpuech O,Rooney C,Mooney L,Baker D,Shaw R,Dymond M,Wang D,Zhang P,Cross S,Veldman-Jones M,Wilson J,Davies BR,Dry JR,Kilgour E,Smith PD

更新日期：2016-11-01 00:00:00

abstract：:Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the United States. Aggressive treatment regimens have not changed the disease course, and the median survival has just recently reached a year. Several mechanisms are proposed to play a role in PDAC therapeutic resistanc...

journal_title：Molecular cancer therapeutics

authors： Logsdon DP,Grimard M,Luo M,Shahda S,Jiang Y,Tong Y,Yu Z,Zyromski N,Schipani E,Carta F,Supuran CT,Korc M,Ivan M,Kelley MR,Fishel ML

更新日期：2016-11-01 00:00:00

abstract：:Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor FLIP is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell d...

journal_title：Molecular cancer therapeutics

authors： McLaughlin KA,Nemeth Z,Bradley CA,Humphreys L,Stasik I,Fenning C,Majkut J,Higgins C,Crawford N,Holohan C,Johnston PG,Harrison T,Hanna GG,Butterworth KT,Prise KM,Longley DB

更新日期：2016-10-01 00:00:00

abstract：:Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeu...

journal_title：Molecular cancer therapeutics

authors： Beck TN,Georgopoulos R,Shagisultanova EI,Sarcu D,Handorf EA,Dubyk C,Lango MN,Ridge JA,Astsaturov I,Serebriiskii IG,Burtness BA,Mehra R,Golemis EA

更新日期：2016-10-01 00:00:00

abstract：:Receptor tyrosine kinases (RTK) are key signaling molecules in regulating cancer cell growth and are important cancer drug targets. Despite the success of specific RTK-targeting therapy in certain cancer treatments, the overall response rates are limited to the drug target-stratified populations. We have systematicall...

journal_title：Molecular cancer therapeutics

authors： Sun X,Song Q,He L,Yan L,Liu J,Zhang Q,Yu Q

更新日期：2016-10-01 00:00:00

abstract：:Using a luciferase reporter-based high-throughput chemical library screen and topological data analysis, we identified N-acridine-9-yl-N',N'-dimethylpropane-1,3-diamine (DAPA) as an inhibitor of the inositol requiring kinase 1α (IRE1α)-X-box binding protein-1 (XBP1) pathway of the unfolded protein response. We designe...

journal_title：Molecular cancer therapeutics

authors： Jiang D,Tam AB,Alagappan M,Hay MP,Gupta A,Kozak MM,Solow-Cordero DE,Lum PY,Denko NC,Giaccia AJ,Le QT,Niwa M,Koong AC

更新日期：2016-09-01 00:00:00

abstract：:Cetuximab, an antibody against the EGFR, has shown efficacy in treating head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer, and non-small cell lung cancer (NSCLC). Despite the clinical success of cetuximab, many patients do not respond to cetuximab. Furthermore, virtually all patients who do i...

journal_title：Molecular cancer therapeutics

authors： Iida M,Bahrar H,Brand TM,Pearson HE,Coan JP,Orbuch RA,Flanigan BG,Swick AD,Prabakaran PJ,Lantto J,Horak ID,Kragh M,Salgia R,Kimple RJ,Wheeler DL

更新日期：2016-09-01 00:00:00

abstract：:Recently, pancreatic ductal adenocarcinoma (PDAC) has emerged as one of the most aggressive malignant tumors with the worst prognosis. Previous studies have demonstrated that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is increased in pancreatic cancer and is identified as a diag...

journal_title：Molecular cancer therapeutics

authors： Li L,Chen H,Gao Y,Wang YW,Zhang GQ,Pan SH,Ji L,Kong R,Wang G,Jia YH,Bai XW,Sun B

更新日期：2016-09-01 00:00:00

abstract：:Bifunctional antibody fusion proteins engaging effector T cells for targeted elimination of tumor cells via CD3 binding have shown efficacy in both preclinical and clinical studies. Different from such a polyclonal T-cell recruitment, an alternative concept is to engage only antigen-specific T-cell subsets. Recruitmen...

journal_title：Molecular cancer therapeutics

authors： Schmittnaegel M,Hoffmann E,Imhof-Jung S,Fischer C,Drabner G,Georges G,Klein C,Knoetgen H

更新日期：2016-09-01 00:00:00

abstract：:There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue c...

journal_title：Molecular cancer therapeutics

authors： Musa F,Alard A,David-West G,Curtin JP,Blank SV,Schneider RJ

更新日期：2016-07-01 00:00:00

abstract：:The epithelial-mesenchymal transition (EMT) is an important mechanism of resistance to angiogenesis inhibition. The ability of EMT pathway genetic variants to predict the efficacy of antiangiogenic therapy is unknown. We analyzed associations between functional SNPs in EMT-related genes and outcomes in metastatic colo...

journal_title：Molecular cancer therapeutics

authors： Matsusaka S,Zhang W,Cao S,Hanna DL,Sunakawa Y,Sebio A,Ueno M,Yang D,Ning Y,Parekh A,Okazaki S,Berger MD,Ichikawa W,Mizunuma N,Lenz HJ

更新日期：2016-06-01 00:00:00

abstract：:Epigenetic abnormalities are common in hematologic malignancies, including multiple myeloma, and their effects can be efficiently counteracted by a class of tumor suppressor miRNAs, named epi-miRNAs. Given the oncogenic role of histone deacetylases (HDAC) in multiple myeloma, we investigated whether their activity cou...

journal_title：Molecular cancer therapeutics

authors： Amodio N,Stamato MA,Gullà AM,Morelli E,Romeo E,Raimondi L,Pitari MR,Ferrandino I,Misso G,Caraglia M,Perrotta I,Neri A,Fulciniti M,Rolfo C,Anderson KC,Munshi NC,Tagliaferri P,Tassone P

更新日期：2016-06-01 00:00:00

abstract：:Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a libra...

journal_title：Molecular cancer therapeutics

authors： Alvero AB,Heaton A,Lima E,Pitruzzello M,Sumi N,Yang-Hartwich Y,Cardenas C,Steinmacher S,Silasi DA,Brown D,Mor G

更新日期：2016-06-01 00:00:00

abstract：:Inhibition of both the de novo (DNP) and salvage (NSP) pathways of nucleoside synthesis has been demonstrated to impair leukemia cells. We endeavored to determine whether this approach would be efficacious in glioblastoma. To diminish nucleoside biosynthesis, we utilized compound DI-39, which selectively targets NSP, ...

journal_title：Molecular cancer therapeutics

authors： Laks DR,Ta L,Crisman TJ,Gao F,Coppola G,Radu CG,Nathanson DA,Kornblum HI

更新日期：2016-06-01 00:00:00

abstract：:Leukemia cells escape BCR-ABL-targeted therapy by developing mutations, such as T315I, in the p210(BCR-ABL) fusion protein in Philadelphia chromosome-positive chronic myeloid leukemia (CML). Although most effort has been focused on development of new tyrosine kinase inhibitors, enrichment of these small-molecule inhib...

journal_title：Molecular cancer therapeutics

authors： Mu C,Wu X,Ma H,Tao W,Zhang G,Xia X,Shen J,Mai J,Sun T,Sun X,Arlinghaus RB,Shen H

更新日期：2016-05-01 00:00:00

abstract：:Multiple myeloma remains incurable and the majority of patients die within 5 years of diagnosis. Reolysin, the infusible form of human reovirus (RV), is a novel viral oncolytic therapy associated with antitumor activity likely resulting from direct oncolysis and a virus-mediated antitumor immune response. Results from...

journal_title：Molecular cancer therapeutics

authors： Stiff A,Caserta E,Sborov DW,Nuovo GJ,Mo X,Schlotter SY,Canella A,Smith E,Badway J,Old M,Jaime-Ramirez AC,Yan P,Benson DM,Byrd JC,Baiocchi R,Kaur B,Hofmeister CC,Pichiorri F

更新日期：2016-05-01 00:00:00

abstract：:A quaternary ammonium-based drug-linker has been developed to expand the scope of antibody-drug conjugate (ADC) payloads to include tertiary amines, a functional group commonly present in biologically active compounds. The linker strategy was exemplified with a β-glucuronidase-cleavable auristatin E construct. The dru...

journal_title：Molecular cancer therapeutics

authors： Burke PJ,Hamilton JZ,Pires TA,Setter JR,Hunter JH,Cochran JH,Waight AB,Gordon KA,Toki BE,Emmerton KK,Zeng W,Stone IJ,Senter PD,Lyon RP,Jeffrey SC

更新日期：2016-05-01 00:00:00

abstract：:Karyopherin beta 1 (Kpnβ1) is a nuclear transport receptor that imports cargoes into the nucleus. Recently, elevated Kpnβ1 expression was found in certain cancers and Kpnβ1 silencing with siRNA was shown to induce cancer cell death. This study aimed to identify novel small molecule inhibitors of Kpnβ1, and determine t...

journal_title：Molecular cancer therapeutics

authors： van der Watt PJ,Chi A,Stelma T,Stowell C,Strydom E,Carden S,Angus L,Hadley K,Lang D,Wei W,Birrer MJ,Trent JO,Leaner VD

更新日期：2016-04-01 00:00:00

abstract：:eIF4E is the key regulator of protein translation and critical for translation. The oncogenic potential of tumorigenesis, which is highly contingent on cap-dependent eIF4E, also arises from the critical role in the nuclear export and cytosolic translation of oncogenic transcripts. Inhibition of Exportin1 (XPO1), which...

journal_title：Molecular cancer therapeutics

authors： Li S,Fu J,Lu C,Mapara MY,Raza S,Hengst U,Lentzsch S

更新日期：2016-04-01 00:00:00