Single-chain antibody-based immunotoxins targeting Her2/neu: design optimization and impact of affinity on antitumor efficacy and off-target toxicity.

abstract：:DNA cytosine methylation plays a considerable role in normal development, gene regulation, and carcinogenesis. Hypermethylation of the promoters of some tumor suppressor genes and the associated silencing of these genes often occur in certain cancer types. The reversal of this process by DNA methylation inhibitors is ...

journal_title：Molecular cancer therapeutics

authors： Chuang JC,Yoo CB,Kwan JM,Li TW,Liang G,Yang AS,Jones PA

更新日期：2005-10-01 00:00:00

abstract：:Acquired resistance severely hinders the application of small-molecule inhibitors. Our understanding of acquired resistance related to FGFRs is limited. Here, to explore the underlying mechanism of acquired resistance in FGFR-aberrant cancer cells, we generated cells resistant to multiple FGFR inhibitors (FGFRi) and i...

journal_title：Molecular cancer therapeutics

authors： Wang X,Ai J,Liu H,Peng X,Chen H,Chen Y,Su Y,Shen A,Huang X,Ding J,Geng M

更新日期：2019-03-01 00:00:00

abstract：:Clinical circumvention of multidrug resistance (MDR) is a Sisyphian task faced in the treatment of many cancers. Identification of several mechanisms of acquired MDR has led to the development of chemosensitizing agents that counter specific mechanisms of MDR. Initial successes in therapy using "chemosensitizers" ofte...

journal_title：Molecular cancer therapeutics

authors： Shain KH,Dalton WS

更新日期：2001-11-01 00:00:00

abstract：:Chronic myelogenous leukemia is characterized by the presence of the chimeric BCR-ABL gene, which is expressed as the constitutively active Bcr-Abl kinase. Although kinase activity is directly responsible for the clinical phenotype, current diagnostic and prognostic methods focus on a genetic classification system in ...

journal_title：Molecular cancer therapeutics

authors： Sylvester JE,Kron SJ

更新日期：2010-05-01 00:00:00

abstract：:RAD51 is a key protein in the homologous recombination (HR) pathway of DNA double-strand break repair, and HR represents a novel target for cancer therapy. Because imatinib (Gleevec) has been reported to reduce RAD51 protein levels, we tested the clonogenic survival for RT112, H1299, PANC1, and PC3 tumor cell lines of...

journal_title：Molecular cancer therapeutics

authors： Choudhury A,Zhao H,Jalali F,Al Rashid S,Ran J,Supiot S,Kiltie AE,Bristow RG

更新日期：2009-01-01 00:00:00

abstract：:The oncogenic beta-catenin/T-cell factor (TCF) signal is a common trigger inducing expressions of various cancer-related genes and is activated in various types of human malignancy. The aim of this study was to create an effective double-stranded DNA decoy that would interfere with endogenous TCF hyperactivity in tumo...

journal_title：Molecular cancer therapeutics

authors： Seki Y,Yamamoto H,Ngan CY,Yasui M,Tomita N,Kitani K,Takemasa I,Ikeda M,Sekimoto M,Matsuura N,Albanese C,Kaneda Y,Pestell RG,Monden M

更新日期：2006-04-01 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：:Colorectal cancer is the second leading cause of cancer mortality in the United States. Substantial human and animal data support the ability of nonsteroidal anti-inflammatory drugs to cause regression of existing colon tumors and prevent new tumor formation. The mechanism by which the nonsteroidal anti-inflammatory d...

journal_title：Molecular cancer therapeutics

authors： Rice PL,Peters SL,Beard KS,Ahnen DJ

更新日期：2006-03-01 00:00:00

abstract：:Invasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis, resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, kisspeptin (KISS1), and i...

journal_title：Molecular cancer therapeutics

authors： Kang HS,Baba T,Mandai M,Matsumura N,Hamanishi J,Kharma B,Kondoh E,Yoshioka Y,Oishi S,Fujii N,Murphy SK,Konishi I

更新日期：2011-04-01 00:00:00

abstract：:CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214, a C3-(isopropylmethoxy)-fused pyrrolocarbazole with potent pan-vascular endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has recently completed phase I clinical trials in cancer patients. These studies evaluated the...

journal_title：Molecular cancer therapeutics

authors： Jones-Bolin S,Zhao H,Hunter K,Klein-Szanto A,Ruggeri B

更新日期：2006-07-01 00:00:00

abstract：:Tamoxifen, a selective estrogen receptor (ER) modulator, is the most widely prescribed hormonal therapy treatment for breast cancer. Despite the benefits of tamoxifen therapy, almost all tamoxifen-responsive breast cancer patients develop resistance to therapy. In addition, tamoxifen displays estrogen-like effects in ...

journal_title：Molecular cancer therapeutics

authors： Shah YM,Al-Dhaheri M,Dong Y,Ip C,Jones FE,Rowan BG

更新日期：2005-08-01 00:00:00

abstract：:At the present time, the optimal development of molecularly targeted anticancer agents is limited by the lack of clinically applicable tools to predict drug effects. This study aimed to develop methods that might be useful in predicting the efficacy of targeted agents in a novel model system of human pancreatic cancer...

journal_title：Molecular cancer therapeutics

authors： Rubio-Viqueira B,Mezzadra H,Nielsen ME,Jimeno A,Zhang X,Iacobuzio-Donahue C,Maitra A,Hidalgo M,Altiok S

更新日期：2007-02-01 00:00:00

abstract：:Rapamycin and its analogues are being tested as new antitumor agents. Rapamycin binds to FKBP-12 and this complex inhibits the activity of FRAP/mammalian target of rapamycin, which leads to dephosphorylation of 4EBP1 and p70 S6 kinase, resulting in blockade of translation initiation. We have found that RAP inhibits th...

journal_title：Molecular cancer therapeutics

authors： García-Morales P,Hernando E,Carrasco-García E,Menéndez-Gutierrez MP,Saceda M,Martínez-Lacaci I

更新日期：2006-09-01 00:00:00

abstract：:Complexities in treating breast cancer with bone metastasis are enhanced by a vicious protumorigenic pathology, involving a shift in skeletal homeostasis toward aggressive osteoclast activity and polarization of immune cells supporting tumor growth and immunosuppression. Recent studies signify the role of receptor act...

journal_title：Molecular cancer therapeutics

authors： Wang H,Ashton R,Hensel JA,Lee JH,Khattar V,Wang Y,Deshane JS,Ponnazhagan S

更新日期：2020-12-01 00:00:00

abstract：:In bone metastatic lesions, osteoclasts play a key role in the development of osteolysis. Previous studies have shown that macrophage colony-stimulating factor (M-CSF) is important for the differentiation of osteoclasts. In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclas...

journal_title：Molecular cancer therapeutics

authors： Ohno H,Kubo K,Murooka H,Kobayashi Y,Nishitoba T,Shibuya M,Yoneda T,Isoe T

更新日期：2006-11-01 00:00:00

abstract：:Human epidermal growth factor receptor-2 (HER2) and epidermal growth factor receptor (EGFR) heterodimerize to activate mitogenic signaling pathways. We have shown previously, using MCF7 subcloned cell lines with graded levels of HER2 expression, that responsiveness to trastuzumab and AG1478 (an anti-EGFR agent), varie...

journal_title：Molecular cancer therapeutics

authors： Emlet DR,Brown KA,Kociban DL,Pollice AA,Smith CA,Ong BB,Shackney SE

更新日期：2007-10-01 00:00:00

abstract：:Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy with one of the worst outcomes among all cancers. PDA often recurs after initial treatment to result in patient death despite the use of chemotherapy or radiation therapy. PDA contains a subset of tumor-initiating cells capable of extensive self-renewa...

journal_title：Molecular cancer therapeutics

authors： Rajeshkumar NV,Rasheed ZA,García-García E,López-Ríos F,Fujiwara K,Matsui WH,Hidalgo M

更新日期：2010-09-01 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：:The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that exists in two complexes (mTORC1 and mTORC2) and integrates extracellular and intracellular signals to act as a master regulator of cell growth, survival, and metabolism. The PI3K/AKT/mTOR prosurvival pathway is often dysregulated in mul...

journal_title：Molecular cancer therapeutics

authors： Slotkin EK,Patwardhan PP,Vasudeva SD,de Stanchina E,Tap WD,Schwartz GK

更新日期：2015-02-01 00:00:00

abstract：:Ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and inhibition of cyclooxygenase-2 (COX2) activity by nonsteroidal anti-inflammatory drugs (NSAID) can both attenuate skin tumorigenesis. The present study examined the hypothesis that combining ligand activation of PPARβ/δ with inhibition o...

journal_title：Molecular cancer therapeutics

authors： Zhu B,Bai R,Kennett MJ,Kang BH,Gonzalez FJ,Peters JM

更新日期：2010-12-01 00:00:00

abstract：:Targeted thrombotic eradication of solid tumors is a novel therapeutic strategy. The feasibility, efficacy, selectivity, and safety are dependent on multiple variables of protein design, molecular assembly, vascular target, and exclusive restriction of function to the tumor vasculature. To advance this strategy, we de...

journal_title：Molecular cancer therapeutics

authors： Liu C,Dickinson C,Shobe J,Doñate F,Ruf W,Edgington T

更新日期：2004-07-01 00:00:00

abstract：:The EGF receptor (EGFR) regulates important cellular processes including proliferation, differentiation, and apoptosis. EGFR is frequently overexpressed in a range of cancers and is associated with disease progression and treatment. Clinical studies have shown that EGFR mutations confer tumor sensitivity to tyrosine k...

journal_title：Molecular cancer therapeutics

authors： Wan S,Wright DW,Coveney PV

更新日期：2012-11-01 00:00:00

abstract：:The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-R...

journal_title：Molecular cancer therapeutics

authors： Ducker CE,Griffel LK,Smith RA,Keller SN,Zhuang Y,Xia Z,Diller JD,Smith CD

更新日期：2006-07-01 00:00:00

abstract：:HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC) composed of the HER3 antibody patritumab and a novel topoisomerase I in...

journal_title：Molecular cancer therapeutics

authors： Koganemaru S,Kuboki Y,Koga Y,Kojima T,Yamauchi M,Maeda N,Kagari T,Hirotani K,Yasunaga M,Matsumura Y,Doi T

更新日期：2019-11-01 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：:R-roscovitine (seliciclib, CYC202) is a cyclin-dependent kinase inhibitor currently in phase II clinical trials in patients with cancer. Here, we describe its mouse metabolism and pharmacokinetics as well as the identification of the principal metabolites in hepatic microsomes, plasma, and urine. Following microsomal ...

journal_title：Molecular cancer therapeutics

authors： Nutley BP,Raynaud FI,Wilson SC,Fischer PM,Hayes A,Goddard PM,McClue SJ,Jarman M,Lane DP,Workman P

更新日期：2005-01-01 00:00:00

abstract：:Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and EBV is the most important pathogenesis. In this study, we explore the potential that a recombinant adeno-associated virus (rAAV) carrying a fusing gene containing heat shock protein as an adjuvant, EBV latent membrane proteins (LMP1 and LMP2) CTL ...

journal_title：Molecular cancer therapeutics

authors： Pan J,Zhang Q,Zhou J,Ma D,Xiao X,Wang DW

更新日期：2009-09-01 00:00:00

abstract：:TAS-121 is a novel orally active selective covalent inhibitor of the mutant EGFR. We performed preclinical characterization of TAS-121 and compared its efficacy and selectivity for common EGFR mutations (Ex19del and L858R), first- and second- generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance mutation (T7...

journal_title：Molecular cancer therapeutics

authors： Ito K,Nishio M,Kato M,Murakami H,Aoyagi Y,Ohe Y,Okayama T,Hashimoto A,Ohsawa H,Tanaka G,Nonoshita K,Ito S,Matsuo K,Miyadera K

更新日期：2019-05-01 00:00:00

abstract：:Chemoresistance is a major reason that patients with osteosarcoma fail to achieve a lasting chemotherapy response, and it contributes to disease relapse, progression, and death. Human glutathione S-transferase P1 (GSTP1), a phase II detoxification enzyme, contributes to chemoresistance in many cancers. However, the ro...

journal_title：Molecular cancer therapeutics

authors： Huang G,Mills L,Worth LL

更新日期：2007-05-01 00:00:00

abstract：:Camptothecin and Adriamycin are clinically important inhibitors for topoisomerase (Topo) I and Topo II, respectively. The ataxia-telangiectasia mutated (ATM) product is essential for ionizing radiation-induced DNA damage responses, but the role of ATM in Topo poisons-induced checkpoints remains unresolved. We found th...

journal_title：Molecular cancer therapeutics

authors： Siu WY,Lau A,Arooz T,Chow JP,Ho HT,Poon RY

更新日期：2004-05-01 00:00:00