Flex-Hets differentially induce apoptosis in cancer over normal cells by directly targeting mitochondria.

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：:DNA double-strand breaks (DSB) are the most cytotoxic lesions induced by topoisomerase II poisons. Nonhomologous end joining (NHEJ) is a major pathway for DSB repair and requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK catalytic subunit (DNA-PKcs) is structurally similar to PI-3K, which promotes cell su...

journal_title：Molecular cancer therapeutics

authors： Munck JM,Batey MA,Zhao Y,Jenkins H,Richardson CJ,Cano C,Tavecchio M,Barbeau J,Bardos J,Cornell L,Griffin RJ,Menear K,Slade A,Thommes P,Martin NM,Newell DR,Smith GC,Curtin NJ

更新日期：2012-08-01 00:00:00

abstract：:Overexpression or hyperactivation of MDM2 contributes to functional inactivation of wild-type p53 in nearly 50% of tumors. Inhibition of p53 by MDM2 depends on binding between an NH(2)-terminal (residues 16-28) p53 alpha-helical peptide and a hydrophobic pocket on MDM2, presenting an attractive target for development ...

journal_title：Molecular cancer therapeutics

authors： Chen L,Yin H,Farooqi B,Sebti S,Hamilton AD,Chen J

更新日期：2005-06-01 00:00:00

abstract：:Recombinant immunotoxins, consisting of single-chain variable fragments (scFv) genetically fused to polypeptide toxins, represent potentially effective candidates for cancer therapeutics. We evaluated the affinity of various anti-Her2/neu scFv fused to recombinant gelonin (rGel) and its effect on antitumor efficacy an...

journal_title：Molecular cancer therapeutics

authors： Cao Y,Marks JD,Huang Q,Rudnick SI,Xiong C,Hittelman WN,Wen X,Marks JW,Cheung LH,Boland K,Li C,Adams GP,Rosenblum MG

更新日期：2012-01-01 00:00:00

abstract：PURPOSE:Expression of the type 1 insulin-like growth factor receptor (IGF1R) confers adverse prognosis in clear cell renal cell cancer (CC-RCC). We recently showed that IGF1R expression is inhibited by the von Hippel-Lindau (VHL) tumor suppressor, and the IGF1R is up-regulated in CC-RCC, in which VHL is frequently inac...

journal_title：Molecular cancer therapeutics

authors： Yuen JS,Akkaya E,Wang Y,Takiguchi M,Peak S,Sullivan M,Protheroe AS,Macaulay VM

更新日期：2009-06-01 00:00:00

abstract：:Enhancer of zester homolog 2 (EZH2), a histone lysine methyltransferase and the catalytic component of polycomb repressive complex 2, has been extensively investigated as a chromatin regulator and a transcriptional suppressor by methylating H3 at lysine 27 (H3K27). EZH2 is upregulated or mutated in most cancers, and i...

journal_title：Molecular cancer therapeutics

authors： Li Q,Liu KY,Liu Q,Wang G,Jiang W,Meng Q,Yi Y,Yang Y,Wang R,Zhu S,Li C,Wu L,Zhao D,Yan L,Zhang L,Kim JS,Zu X,Kozielski AJ,Qian W,Chang JC,Patnaik A,Chen K,Cao Q

更新日期：2020-10-01 00:00:00

abstract：:Malignant ascitis (MA) is a highly intractable and immunotherapy-resistant state of advanced gastrointestinal and ovarian cancers. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryr...

journal_title：Molecular cancer therapeutics

authors： Sugiyama M,Kakeji Y,Tsujitani S,Harada Y,Onimaru M,Yoshida K,Tanaka S,Emi Y,Morita M,Morodomi Y,Hasegawa M,Maehara Y,Yonemitsu Y

更新日期：2011-03-01 00:00:00

abstract：:Histone deacetylase inhibitors have emerged as promising anticancer drugs. Using an unbiased ultrahigh throughput screening system, a novel mercaptoketone-based histone deacetylase inhibitor series was identified that was optimized to the lead compound, KD5170. KD5170 inhibited the proliferation of myeloma cell lines ...

journal_title：Molecular cancer therapeutics

authors： Feng R,Ma H,Hassig CA,Payne JE,Smith ND,Mapara MY,Hager JH,Lentzsch S

更新日期：2008-06-01 00:00:00

abstract：:The camptothecin derivatives topoisomerase I (TOP1) inhibitors, irinotecan and topotecan, are FDA approved for the treatment of colorectal, ovarian, lung and breast cancers. Because of the chemical instability of camptothecins, short plasma half-life, drug efflux by the multidrug-resistance ABC transporters, and the s...

journal_title：Molecular cancer therapeutics

authors： Marzi L,Sun Y,Huang SN,James A,Difilippantonio S,Pommier Y

更新日期：2020-08-01 00:00:00

abstract：:The type I EGF receptor (EGFR or ErbB1) and insulin-like growth factor-binding protein-3 (IGFBP-3) are highly expressed in triple-negative breast cancer (TNBC), a particularly aggressive disease that cannot be treated with conventional therapies targeting the estrogen or progesterone receptors (ER and PR), or HER2. We...

journal_title：Molecular cancer therapeutics

authors： Martin JL,de Silva HC,Lin MZ,Scott CD,Baxter RC

更新日期：2014-02-01 00:00:00

abstract：:Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer treated with adjuvant chemotherapy. Genetic single-nucleotide polymorphisms (SNP) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future dr...

journal_title：Molecular cancer therapeutics

authors： Ning Y,Gerger A,Zhang W,Hanna DL,Yang D,Winder T,Wakatsuki T,Labonte MJ,Stintzing S,Volz N,Sunakawa Y,Stremitzer S,El-Khoueiry R,Lenz HJ

更新日期：2014-02-01 00:00:00

abstract：:Bortezomib combination with gemcitabine/cisplatin in patients with advanced tumors, predominantly non-small cell lung cancer (NSCLC), showed an unexpected transient drop in the deoxycytidine plasma levels, a marker for gemcitabine activity. This study investigates the pharmacokinetic/pharmacodynamic effect of bortezom...

journal_title：Molecular cancer therapeutics

authors： Ceresa C,Giovannetti E,Voortman J,Laan AC,Honeywell R,Giaccone G,Peters GJ

更新日期：2009-05-01 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：:The PI3K pathway is considered a master regulator for cancer due to its frequent activation, making it an attractive target for pharmacologic intervention. While substantial efforts have been made to develop drugs targeting PI3K signaling, few drugs have been able to achieve the inhibition necessary for effective tumo...

journal_title：Molecular cancer therapeutics

authors： Perino S,Moreau B,Freda J,Cirello A,White BH,Quinn JM,Kriksciukaite K,Someshwar A,Romagnoli J,Robinson M,Movassaghian S,Cipriani T,Wooster R,Bilodeau MT,Whalen KA

更新日期：2020-08-01 00:00:00

abstract：:Several caged Garcinia xanthone natural products have potent bioactivity and a documented value in traditional Eastern medicine. Previous synthesis and structure activity relationship studies of these natural products resulted in the identification of the pharmacophore represented by the structure of cluvenone. In the...

journal_title：Molecular cancer therapeutics

authors： Batova A,Altomare D,Chantarasriwong O,Ohlsen KL,Creek KE,Lin YC,Messersmith A,Yu AL,Yu J,Theodorakis EA

更新日期：2010-11-01 00:00:00

abstract：:Genital human papillomavirus (HPV) infection is the primary cause of cervical cancer in women. Although the HPV recombinant L1 protein was recently licensed as an available vaccine, it has numerous shortcomings. New vaccination strategies should be considered. To enable the design of a prophylactic and therapeutic low...

journal_title：Molecular cancer therapeutics

authors： Bian T,Wang Y,Lu Z,Ye Z,Zhao L,Ren J,Zhang H,Ruan L,Tian H

更新日期：2008-05-01 00:00:00

abstract：:SJG-136 is a new pyrrolobenzodiazepine dimer inducing time-dependent cytotoxicity. HCT 116 cells were exposed to 50 nmol/L of SJG-136 for 1 hour or 1 nmol/L of SJG-136 for 24 hours to achieve similar levels of interstrand cross-links (ICL). The short exposure led to a rapid formation of ICLs (1 hour), early H2AX foci ...

journal_title：Molecular cancer therapeutics

authors： Arnould S,Spanswick VJ,Macpherson JS,Hartley JA,Thurston DE,Jodrell DI,Guichard SM

更新日期：2006-06-01 00:00:00

abstract：:Soft-tissue sarcomas (STS) represent a heterogeneous group of rare, malignant tumors of mesenchymal origin. Reliable in vivo sarcoma research models are scarce. We aimed to establish and characterize histologically and molecularly stable patient-derived xenograft (PDX) models from a broad variety of STS subtypes. A to...

journal_title：Molecular cancer therapeutics

authors： Cornillie J,Wozniak A,Li H,Wang Y,Boeckx B,Gebreyohannes YK,Wellens J,Vanleeuw U,Hompes D,Stas M,Sinnaeve F,Wafa H,Lambrechts D,Debiec-Rychter M,Sciot R,Schöffski P

更新日期：2019-06-01 00:00:00

abstract：:Epithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a p...

journal_title：Molecular cancer therapeutics

authors： Figueras A,Alsina-Sanchís E,Lahiguera Á,Abreu M,Muinelo-Romay L,Moreno-Bueno G,Casanovas O,Graupera M,Matias-Guiu X,Vidal A,Villanueva A,Viñals F

更新日期：2018-02-01 00:00:00

abstract：:Pulmonary metastasis is the most significant prognostic determinant for osteosarcoma, but methods for its prediction and treatment have not been established. Using oligonucleotide microarrays, we compared the global gene expression of biopsy samples between seven osteosarcoma patients who developed pulmonary metastasi...

journal_title：Molecular cancer therapeutics

authors： Kobayashi E,Masuda M,Nakayama R,Ichikawa H,Satow R,Shitashige M,Honda K,Yamaguchi U,Shoji A,Tochigi N,Morioka H,Toyama Y,Hirohashi S,Kawai A,Yamada T

更新日期：2010-03-01 00:00:00

abstract：:Long noncoding RNAs (lncRNA) have been found to play critical roles in tumorigenesis and the development of various cancers, including hepatocellular carcinoma (HCC). Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) has been identified as an oncogene and prognostic biomarker in HCC. Here, we demons...

journal_title：Molecular cancer therapeutics

authors： Fan L,Huang X,Chen J,Zhang K,Gu YH,Sun J,Cui SY

更新日期：2020-05-01 00:00:00

abstract：:Mithramycin A is a DNA-binding antitumor agent, which has been clinically used in the therapies of several types of cancer and Paget's disease. In this study, we investigated the combined effect of mithramycin A and tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) on apoptosis of cancer cells. In ...

journal_title：Molecular cancer therapeutics

authors： Lee TJ,Jung EM,Lee JT,Kim S,Park JW,Choi KS,Kwon TK

更新日期：2006-11-01 00:00:00

abstract：:A novel oral Hsp90 inhibitor, NVP-HSP990, has been developed and characterized in vitro and in vivo. In vitro, NVP-HSP990 exhibits single digit nanomolar IC(50) values on three of the Hsp90 isoforms (Hsp90α, Hsp90β, and GRP94) and 320 nanomolar IC(50) value on the fourth (TRAP-1), with selectivity against unrelated en...

journal_title：Molecular cancer therapeutics

authors： Menezes DL,Taverna P,Jensen MR,Abrams T,Stuart D,Yu GK,Duhl D,Machajewski T,Sellers WR,Pryer NK,Gao Z

更新日期：2012-03-01 00:00:00

abstract：:Deregulation of the cell cycle has long been recognized as an essential driver of tumorigenesis, and agents that selectively target key cell cycle components continue to hold promise as potential therapeutics. We have developed AZD5438, a 4-(1-isopropyl-2-methylimidazol-5-yl)-2-(4-methylsulphonylanilino) pyrimidine, a...

journal_title：Molecular cancer therapeutics

authors： Byth KF,Thomas A,Hughes G,Forder C,McGregor A,Geh C,Oakes S,Green C,Walker M,Newcombe N,Green S,Growcott J,Barker A,Wilkinson RW

更新日期：2009-07-01 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：:Acquired resistance to cancer drugs is common, also for modern targeted drugs like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, a new drug approved for the treatment of the highly aggressive and relapsing mantle cell lymphoma (MCL). The tumor microenvironment often impacts negatively on drug response. Here, w...

journal_title：Molecular cancer therapeutics

authors： Guan J,Huang D,Yakimchuk K,Okret S

更新日期：2018-05-01 00:00:00

abstract：:Constitutive activation of Janus kinases (JAKs) and signal transducers and activators of transcription (STAT) occurs at very high frequency in various hematopoietic malignancies and solid tumors. It has been demonstrated that the tyrosine kinase inhibitor, AG-490, selectively blocks JAK activity and completely elimina...

journal_title：Molecular cancer therapeutics

authors： Burdelya L,Catlett-Falcone R,Levitzki A,Cheng F,Mora LB,Sotomayor E,Coppola D,Sun J,Sebti S,Dalton WS,Jove R,Yu H

更新日期：2002-09-01 00:00:00

abstract：:Uveal melanoma is a rare and aggressive cancer that originates in the eye. Currently, there are no approved targeted therapies and very few effective treatments for this cancer. Although activating mutations in the G protein alpha subunits, GNAQ and GNA11, are key genetic drivers of the disease, few additional drug ta...

journal_title：Molecular cancer therapeutics

authors： Rago F,Elliott G,Li A,Sprouffske K,Kerr G,Desplat A,Abramowski D,Chen JT,Farsidjani A,Xiang KX,Bushold G,Feng Y,Shirley MD,Bric A,Vattay A,Möbitz H,Nakajima K,Adair CD,Mathieu S,Ntaganda R,Smith T,Papillon JPN,

更新日期：2020-10-01 00:00:00

abstract：:Vascular endothelial growth factor (VEGF)-induced endothelial cell migration is an important component of tumor angiogenesis. Rho and Rho-associated kinase (ROCK) are key regulators of focal adhesion, stress fiber formation, and thus cell motility. Inhibitors of this pathway have been shown to inhibit endothelial cell...

journal_title：Molecular cancer therapeutics

authors： Yin L,Morishige K,Takahashi T,Hashimoto K,Ogata S,Tsutsumi S,Takata K,Ohta T,Kawagoe J,Takahashi K,Kurachi H

更新日期：2007-05-01 00:00:00

abstract：:Anti-HER2/CD3, a T-cell-dependent bispecific antibody (TDB) construct, induces T-cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic synapse. TDB design is a very challenging process that requires consideration of m...

journal_title：Molecular cancer therapeutics

authors： Mandikian D,Takahashi N,Lo AA,Li J,Eastham-Anderson J,Slaga D,Ho J,Hristopoulos M,Clark R,Totpal K,Lin K,Joseph SB,Dennis MS,Prabhu S,Junttila TT,Boswell CA

更新日期：2018-04-01 00:00:00