Evading Pgp activity in drug-resistant cancer cells: a structural and functional study of antitubulin furan metotica compounds.

abstract：:Mitotic spindle poisons (e.g., Taxol and vinblastine), used as chemotherapy drugs, inhibit mitotic spindle function, activate the mitotic spindle checkpoint, arrest cells in mitosis, and then cause cell death by mechanisms that are poorly understood. By expression cloning, we identified a truncated version of human TR...

journal_title：Molecular cancer therapeutics

authors： Yamada HY,Gorbsky GJ

更新日期：2006-01-01 00:00:00

abstract：:Betulinic acid (BA), a pentacyclic triterpene isolated from birch bark and other plants, selectively inhibits the growth of human cancer cell lines. However, the poor potency of BA hinders its clinical development, despite a lack of toxicity in animal studies even at high concentrations. Here, we describe six BA deriv...

journal_title：Molecular cancer therapeutics

authors： Liby K,Honda T,Williams CR,Risingsong R,Royce DB,Suh N,Dinkova-Kostova AT,Stephenson KK,Talalay P,Sundararajan C,Gribble GW,Sporn MB

更新日期：2007-07-01 00:00:00

abstract：:Labetuzumab govitecan (IMMU-130), an antibody-drug conjugate (ADC) with an average of 7.6 SN-38/IgG, was evaluated for its potential to enhance delivery of SN-38 to human colonic tumor xenografts. Mice bearing LS174T or GW-39 human colonic tumor xenografts were injected with irinotecan or IMMU-130 (SN-38 equivalents ∼...

journal_title：Molecular cancer therapeutics

authors： Sharkey RM,Govindan SV,Cardillo TM,Donnell J,Xia J,Rossi EA,Chang CH,Goldenberg DM

更新日期：2018-01-01 00:00:00

abstract：:Soluble copolymers of camptothecin (CPT), based on poly[N-(2-hydroxypropyl) methacrylamide] (pHPMA), were obtained by conjugation through the degradable spacers -Gly-Phe-Leu-Gly- or -Gly-6-aminohexanoyl-Gly-. We investigated to what extent passive accumulation and retention of hydroxypropyl methacrylamide copolymer of...

journal_title：Molecular cancer therapeutics

authors： Zamai M,VandeVen M,Farao M,Gratton E,Ghiglieri A,Castelli MG,Fontana E,D'Argy R,Fiorino A,Pesenti E,Suarato A,Caiolfa VR

更新日期：2003-01-01 00:00:00

abstract：:Amplification of human epidermal growth factor receptor 2 (HER2) has been detected in 20% to 30% of gastric cancers and is associated with a poor outcome. Combination therapies with HER2-targeting agents and cytotoxic agents are considered a potential therapeutic option for gastric cancer with HER2 amplification. We h...

journal_title：Molecular cancer therapeutics

authors： Tanizaki J,Okamoto I,Takezawa K,Tsukioka S,Uchida J,Kiniwa M,Fukuoka M,Nakagawa K

更新日期：2010-05-01 00:00:00

abstract：:Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single-sh...

journal_title：Molecular cancer therapeutics

authors： Naik S,Galyon GD,Jenks NJ,Steele MB,Miller AC,Allstadt SD,Suksanpaisan L,Peng KW,Federspiel MJ,Russell SJ,LeBlanc AK

更新日期：2018-01-01 00:00:00

abstract：:Mutations in ERK signaling drive a significant percentage of malignancies. LY3009120, a pan-RAF and dimer inhibitor, has preclinical activity in RAS- and BRAF-mutated cell lines including BRAF-mutant melanoma resistant to BRAF inhibitors. This multicenter, open-label, phase I clinical trial (NCT02014116) consisted of ...

journal_title：Molecular cancer therapeutics

authors： Sullivan RJ,Hollebecque A,Flaherty KT,Shapiro GI,Rodon Ahnert J,Millward MJ,Zhang W,Gao L,Sykes A,Willard MD,Yu D,Schade AE,Crowe K,Flynn DL,Kaufman MD,Henry JR,Peng SB,Benhadji KA,Conti I,Gordon MS,Tiu RV,Hong

更新日期：2020-02-01 00:00:00

abstract：:Melanoma is a highly metastatic and deadly disease. An agent simultaneously targeting the COX-2, PI3K/Akt, and mitogen-activated protein kinase (MAPK) signaling pathways that are deregulated in up to 70% of sporadic melanomas might be an effective treatment, but no agent of this type exists. To develop a single drug i...

journal_title：Molecular cancer therapeutics

authors： Gowda R,Madhunapantula SV,Desai D,Amin S,Robertson GP

更新日期：2013-01-01 00:00:00

abstract：:PI3K is frequently mutated in cancer and plays an important role in cell growth and survival. Heregulin (HRG)-mediated autocrine or paracrine signaling through the receptor tyrosine kinase ErbB3 potently activates the PI3K/AKT pathway and has been shown to mediate resistance to a wide variety of anticancer agents. Alt...

journal_title：Molecular cancer therapeutics

authors： Yarar D,Lahdenranta J,Kubasek W,Nielsen UB,MacBeath G

更新日期：2015-09-01 00:00:00

abstract：:Insulin-like growth factor-I receptor (IGF-IR) is an important mediator of tumor cell survival and shows prognostic significance in sarcoma. To explore potential therapeutic strategies for interrupting signaling through this pathway, we assessed the ability of cyclolignan picropodophyllin (PPP), a member of the cyclol...

journal_title：Molecular cancer therapeutics

authors： Duan Z,Choy E,Harmon D,Yang C,Ryu K,Schwab J,Mankin H,Hornicek FJ

更新日期：2009-08-01 00:00:00

abstract：:Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC). While in clinical trials, PF02341066 has shown a significan...

journal_title：Molecular cancer therapeutics

authors： Sun Y,Nowak KA,Zaorsky NG,Winchester CL,Dalal K,Giacalone NJ,Liu N,Werner-Wasik M,Wasik MA,Dicker AP,Lu B

更新日期：2013-05-01 00:00:00

abstract：:RX-5902 is a first-in-class anticancer agent targeting phosphorylated-p68 and attenuating nuclear shuttling of β-catenin. The purpose of this study was to evaluate the efficacy of RX-5902 in preclinical models of triple-negative breast cancer (TNBC) and to explore effects on β-catenin expression. A panel of 18 TNBC ce...

journal_title：Molecular cancer therapeutics

authors： Capasso A,Bagby SM,Dailey KL,Currimjee N,Yacob BW,Ionkina A,Frank JG,Kim DJ,George C,Lee YB,Benaim E,Gittleman B,Hartman SJ,Tan AC,Kim J,Pitts TM,Eckhardt SG,Tentler JJ,Diamond JR

更新日期：2019-11-01 00:00:00

abstract：:TRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasm...

journal_title：Molecular cancer therapeutics

authors： Liu Y,Starr MD,Brady JC,Rushing C,Pang H,Adams B,Alvarez D,Theuer CP,Hurwitz HI,Nixon AB

更新日期：2018-10-01 00:00:00

abstract：:Cisplatin is a cytotoxic chemotherapeutic drug frequently used to treat many solid tumors, including head and neck squamous cell carcinoma (HNSCC). EGF receptor (EGFR) inhibitors have also shown efficacy as alternatives to cisplatin in some situations. However, large clinical trials have shown no added survival benefi...

journal_title：Molecular cancer therapeutics

authors： Schmitt NC,Trivedi S,Ferris RL

更新日期：2015-09-01 00:00:00

abstract：:The effect of vascular endothelial growth factor (VEGF) ligands and cediranib on tumor cell proliferation, migration, and invasion was determined. It has recently been suggested that autocrine signaling through the VEGF receptor (VEGFR) pathway may play a role in tumor cell survival, invasion, and migration. The purpo...

journal_title：Molecular cancer therapeutics

authors： Morelli MP,Brown AM,Pitts TM,Tentler JJ,Ciardiello F,Ryan A,Jürgensmeier JM,Eckhardt SG

更新日期：2009-09-01 00:00:00

abstract：:Controversy exists surrounding whether heterogeneous disruption of the blood-brain barrier (BBB), as seen in glioblastoma (GBM), leads to adequate drug delivery sufficient for efficacy in GBM. This question is especially important when using potent, targeted agents that have a poor penetration across an intact BBB. Ef...

journal_title：Molecular cancer therapeutics

authors： Kim M,Ma DJ,Calligaris D,Zhang S,Feathers RW,Vaubel RA,Meaux I,Mladek AC,Parrish KE,Jin F,Barriere C,Debussche L,Watters J,Tian S,Decker PA,Eckel-Passow JE,Kitange GJ,Johnson AJ,Parney IF,Anastasiadis PZ,Agar NYR

更新日期：2018-09-01 00:00:00

abstract：:Breast cancer resistance to the antiestrogens tamoxifen (OHT) and fulvestrant is accompanied by alterations in both estrogen-dependent and estrogen-independent signaling pathways. Consequently, effective inhibition of both pathways may be necessary to block proliferation of antiestrogen-resistant breast cancer cells. ...

journal_title：Molecular cancer therapeutics

authors： Long X,Fan M,Bigsby RM,Nephew KP

更新日期：2008-07-01 00:00:00

abstract：:Extensive efforts are under way to identify antiangiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGF receptor-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cel...

journal_title：Molecular cancer therapeutics

authors： Hardwick JS,Yang Y,Zhang C,Shi B,McFall R,Koury EJ,Hill SL,Dai H,Wasserman R,Phillips RL,Weinstein EJ,Kohl NE,Severino ME,Lamb JR,Sepp-Lorenzino L

更新日期：2005-03-01 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：:Genomic analyses of squamous cell carcinoma (SCC) have yet to yield significant strategies against pathway activation to improve treatment. Platinum-based chemotherapy remains the mainstay of treatment for SCC of different histotypes either as a single-agent or alongside other chemotherapeutic drugs or radiotherapy; h...

journal_title：Molecular cancer therapeutics

authors： Kong LR,Chua KN,Sim WJ,Ng HC,Bi C,Ho J,Nga ME,Pang YH,Ong WR,Soo RA,Huynh H,Chng WJ,Thiery JP,Goh BC

更新日期：2015-07-01 00:00:00

abstract：:Aberrant DNA methylation patterns play an important role in the pathogenesis of hematologic malignancies. The DNA methyltransferase inhibitors azacytidine and decitabine have shown significant clinical benefits in the treatment of myelodysplastic syndrome (MDS), but their precise mode of action remains to be establish...

journal_title：Molecular cancer therapeutics

authors： Stresemann C,Bokelmann I,Mahlknecht U,Lyko F

更新日期：2008-09-01 00:00:00

abstract：:Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that promotes malignant glioma invasion, angiogenesis, and immunosuppression. Antisense oligonucleotide suppression of TGF-beta(2) ligand expression has shown promise in preclinical and clinical studies but at least two ligands mediate the effect...

journal_title：Molecular cancer therapeutics

authors： Hjelmeland MD,Hjelmeland AB,Sathornsumetee S,Reese ED,Herbstreith MH,Laping NJ,Friedman HS,Bigner DD,Wang XF,Rich JN

更新日期：2004-06-01 00:00:00

abstract：:The secondary T790M mutation in epidermal growth factor receptor (EGFR) is the major mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). Although irreversible EGFR TKIs, such as afatinib or dacomitinib, have been introduced to overcome the acquired resistanc...

journal_title：Molecular cancer therapeutics

authors： Kim SM,Kwon OJ,Hong YK,Kim JH,Solca F,Ha SJ,Soo RA,Christensen JG,Lee JH,Cho BC

更新日期：2012-10-01 00:00:00

abstract：:Aminoflavone (AF), a clinically investigational novel anticancer agent, requires sequential metabolic activation by CYP1A1 and SULT1A1 to exert its antitumor activities. The purpose of this study was to determine the functional significance of common polymorphisms of human CYP1A1 and SULT1A1 on the metabolism and cyto...

journal_title：Molecular cancer therapeutics

authors： Zheng Q,Sha X,Liu J,Heath E,Lorusso P,Li J

更新日期：2010-10-01 00:00:00

abstract：:Prostate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase that is highly expressed in nearly all prostate cancers with the highest expression in metastatic castration-resistant prostate cancer (mCRPC). The prevalence of increased surface expression and constitutive internalization of PSM...

journal_title：Molecular cancer therapeutics

authors： Cho S,Zammarchi F,Williams DG,Havenith CEG,Monks NR,Tyrer P,D'Hooge F,Fleming R,Vashisht K,Dimasi N,Bertelli F,Corbett S,Adams L,Reinert HW,Dissanayake S,Britten CE,King W,Dacosta K,Tammali R,Schifferli K,Strout P

更新日期：2018-10-01 00:00:00

abstract：:We have synthesized several new phenyl maleimide compounds, which are potent growth inhibitors of several human tumor cell lines. Among these, PM-20 was the most potent with an IC50 of 700 nmol/L for Hep3B human hepatoma cell growth. Two other derivatives, PM-26 and PM-38, did not inhibit Hep3B cell growth even at 100...

journal_title：Molecular cancer therapeutics

authors： Kar S,Wang M,Yao W,Michejda CJ,Carr BI

更新日期：2006-06-01 00:00:00

abstract：:Radiotherapy can be synergistically combined with immunotherapy in mouse models, extending its efficacious effects outside of the irradiated field (abscopal effects). We previously reported that a regimen encompassing local radiotherapy in combination with anti-CD137 plus anti-PD-1 mAbs achieves potent abscopal effect...

journal_title：Molecular cancer therapeutics

authors： Rodríguez-Ruiz ME,Rodríguez I,Mayorga L,Labiano T,Barbes B,Etxeberria I,Ponz-Sarvise M,Azpilikueta A,Bolaños E,Sanmamed MF,Berraondo P,Calvo FA,Barcelos-Hoff MH,Perez-Gracia JL,Melero I

更新日期：2019-03-01 00:00:00

abstract：:Molecular mechanisms underlying epothilone-induced apoptotic cell death were investigated in SW620 human colon cancer cells. Treatment with epothilone B and D at different concentrations (1-100 nmol/L) dose-dependently inhibited cell growth and caused cell cycle arrest at G2-M, which was followed by apoptosis. Consist...

journal_title：Molecular cancer therapeutics

authors： Lee SH,Son SM,Son DJ,Kim SM,Kim TJ,Song S,Moon DC,Lee HW,Ryu JC,Yoon DY,Hong JT

更新日期：2007-10-01 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：:Several antiangiogenic drugs targeting VEGF/VEGF receptor (VEGFR) that were approved by the Food and Drug Administration for many cancer types, including colorectal and lung cancer, can effectively reduce tumor growth. However, targeting the VEGF signaling pathway will probably influence the normal function of endothe...

journal_title：Molecular cancer therapeutics

authors： Chen CT,Yamaguchi H,Lee HJ,Du Y,Lee HH,Xia W,Yu WH,Hsu JL,Yen CJ,Sun HL,Wang Y,Yeh ET,Hortobagyi GN,Hung MC

更新日期：2011-08-01 00:00:00