In vitro and in vivo characterization of irreversible mutant-selective EGFR inhibitors that are wild-type sparing.

abstract：:Neuroblastoma is the most common extracranial solid malignancy in the pediatric population, accounting for over 9% of all cancer-related deaths in children. Autophagy is a cell self-protective mechanism that promotes tumor cell growth and survival, making it an attractive target for treating cancer. However, the role ...

journal_title：Molecular cancer therapeutics

authors： Dower CM,Bhat N,Gebru MT,Chen L,Wills CA,Miller BA,Wang HG

更新日期：2018-11-01 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：:The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived canna...

journal_title：Molecular cancer therapeutics

authors： Marcu JP,Christian RT,Lau D,Zielinski AJ,Horowitz MP,Lee J,Pakdel A,Allison J,Limbad C,Moore DH,Yount GL,Desprez PY,McAllister SD

更新日期：2010-01-01 00:00:00

abstract：:The oncoprotein Eps8 facilitates proliferation in fibroblasts and colon cancer cells. However, its role in human cervical cancer is unclear. By immunohistochemical staining and Western blotting, aberrant Eps8 expression was observed in cervical carcinoma compared with normal cervical epithelial cells. Clinicopathologi...

journal_title：Molecular cancer therapeutics

authors： Chen YJ,Shen MR,Chen YJ,Maa MC,Leu TH

更新日期：2008-06-01 00:00:00

abstract：:An ideal therapeutic for cancer would be one that selectively targets to tumor cells, is nontoxic to normal cells, and that could be systemically delivered, thereby reaching metastases as well as primary tumor. Immunoliposomes directed by monoclonal antibody or its fragments are promising vehicles for tumor-targeted d...

journal_title：Molecular cancer therapeutics

authors： Xu L,Huang CC,Huang W,Tang WH,Rait A,Yin YZ,Cruz I,Xiang LM,Pirollo KF,Chang EH

更新日期：2002-03-01 00:00:00

abstract：:Arsenic trioxide (As(2)O(3)) has been used successfully in the treatment of acute promyelocytic leukemia. However, effects of As(2)O(3) in normal peripheral blood T cells have not been studied in detail. The purpose of this study was to investigate whether As(2)O(3) would induce apoptosis in normal T cells and therefo...

journal_title：Molecular cancer therapeutics

authors： Gupta S,Yel L,Kim D,Kim C,Chiplunkar S,Gollapudi S

更新日期：2003-08-01 00:00:00

abstract：:Eribulin (E7389), a synthetic analogue of halichondrin B in phase III clinical trials for breast cancer, binds to tubulin and microtubules. At low concentrations, it suppresses the growth phase of microtubule dynamic instability in interphase cells, arrests mitosis, and induces apoptosis, suggesting that suppression o...

journal_title：Molecular cancer therapeutics

authors： Okouneva T,Azarenko O,Wilson L,Littlefield BA,Jordan MA

更新日期：2008-07-01 00:00:00

abstract：:Activin receptor-like kinase-1 (ALK1) is a type I, endothelial cell-specific member of the transforming growth factor-beta superfamily of receptors known to play an essential role in modulating angiogenesis and vessel maintenance. In the present study, we sought to examine the angiogenic and tumorigenic effects mediat...

journal_title：Molecular cancer therapeutics

authors： Mitchell D,Pobre EG,Mulivor AW,Grinberg AV,Castonguay R,Monnell TE,Solban N,Ucran JA,Pearsall RS,Underwood KW,Seehra J,Kumar R

更新日期：2010-02-01 00:00:00

abstract：:Multiple myeloma is characterized by the malignant proliferating antibody-producing plasma cells in the bone marrow. Despite recent advances in therapy that improve the survival of patients, multiple myeloma remains incurable and therapy resistance is the major factor causing lethality. Clearly, more effective treatme...

journal_title：Molecular cancer therapeutics

authors： Vincenz L,Jäger R,O'Dwyer M,Samali A

更新日期：2013-06-01 00:00:00

abstract：:Bone metastases occur in more than one-third of patients with advanced lung cancer and are difficult to treat. We showed previously the therapeutic effect of a third-generation bisphosphonate, minodronate, and anti-parathyroid hormone-related protein (PTHrP) neutralizing antibody on bone metastases induced by the huma...

journal_title：Molecular cancer therapeutics

authors： Yamada T,Muguruma H,Yano S,Ikuta K,Ogino H,Kakiuchi S,Hanibuchi M,Uehara H,Nishioka Y,Sone S

更新日期：2009-01-01 00:00:00

abstract：:Myeloid-derived suppressor cells (MDSC) are innate immune cells that potently inhibit T cells. In cancer, novel therapies aimed to activate T cells can be rendered ineffective due to the activity of MDSCs. Thus, targeted inhibition of MDSCs may greatly enhance T-cell-mediated antitumor immunity, but mechanisms remain ...

journal_title：Molecular cancer therapeutics

authors： Plebanek MP,Bhaumik D,Bryce PJ,Thaxton CS

更新日期：2018-03-01 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：:We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G2-M arrest, which occurred mainly at the mitotic phase. In addition, immunofluores...

journal_title：Molecular cancer therapeutics

authors： Li PK,Pandit B,Sackett DL,Hu Z,Zink J,Zhi J,Freeman D,Robey RW,Werbovetz K,Lewis A,Li C

更新日期：2006-02-01 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：:Hepatocellular carcinoma is highly chemoresistant, and ATP-binding cassette subfamily G member 2 (ABCG2) is thought to play a critical role in this drug resistance. The present study aims to develop effective therapeutic strategies to decrease ABCG2 expression level and to surmount drug resistance in hepatocellular ca...

journal_title：Molecular cancer therapeutics

authors： Hou H,Sun H,Lu P,Ge C,Zhang L,Li H,Zhao F,Tian H,Zhang L,Chen T,Yao M,Li J

更新日期：2013-12-01 00:00:00

abstract：:Preclinical studies have suggested that VEGFR1-positive cells potentially foster the development of metastases by establishing a "premetastatic niche." We sought to test this hypothesis in high-risk localized prostate cancer and assess potential niche modulation by the VEGFR1-targeting drug axitinib. Formalin-fixed, p...

journal_title：Molecular cancer therapeutics

authors： Pal SK,Vuong W,Zhang W,Deng J,Liu X,Carmichael C,Ruel N,Pinnamaneni M,Twardowski P,Lau C,Yu H,Figlin RA,Agarwal N,Jones JO

更新日期：2015-12-01 00:00:00

abstract：:For a subpopulation of acute myeloid leukemia (AML) patients, the constitutively activated tyrosine kinase, mutant FLT3, has emerged as a promising target for therapy. The development of drug resistance, however, is a growing concern for mutant FLT3 inhibitors, such as PKC412. Potential therapeutic benefit can arise f...

journal_title：Molecular cancer therapeutics

authors： Weisberg E,Choi HG,Barrett R,Zhou W,Zhang J,Ray A,Nelson EA,Jiang J,Moreno D,Stone R,Galinsky I,Fox E,Adamia S,Kung AL,Gray NS,Griffin JD

更新日期：2010-09-01 00:00:00

abstract：:We reported previously a significant increase in survival of nude rats harboring orthotopic A549 human non-small cell lung cancer tumors after treatment with a combination of exisulind (Sulindac Sulfone) and docetaxel (D. C. Chan, Clin. Cancer Res., 8: 904-912, 2002). The purpose of the current study was to determine ...

journal_title：Molecular cancer therapeutics

authors： Whitehead CM,Earle KA,Fetter J,Xu S,Hartman T,Chan DC,Zhao TL,Piazza G,Klein-Szanto AJ,Pamukcu R,Alila H,Bunn PA Jr,Thompson WJ

更新日期：2003-05-01 00:00:00

abstract：:Although both erlotinib and gefitinib target the EGF receptor (EGFR), erlotinib is effective in patients with EGFR wild-type or mutated tumors, whereas gefitinib is only beneficial for patients with activating mutations. To determine whether these differences in clinical outcomes can be attributed to their respective ...

journal_title：Molecular cancer therapeutics

authors： Augustin A,Lamerz J,Meistermann H,Golling S,Scheiblich S,Hermann JC,Duchateau-Nguyen G,Tzouros M,Avila DW,Langen H,Essioux L,Klughammer B

更新日期：2013-04-01 00:00:00

abstract：:Bcl-2 and Bcl-xL are associated with treatment resistance and progression in many cancers, including prostate cancer. The objective of this study was to determine whether a novel bispecific antisense oligonucleotide targeting both Bcl-2 and Bcl-xL induces apoptosis and enhances chemosensitivity in androgen-independent...

journal_title：Molecular cancer therapeutics

authors： Yamanaka K,Rocchi P,Miyake H,Fazli L,Vessella B,Zangemeister-Wittke U,Gleave ME

更新日期：2005-11-01 00:00:00

abstract：:TIGIT is an immune checkpoint inhibitor expressed by effector CD4+ and CD8+ T cells, NK cells, and regulatory T cells (Tregs). Inhibition of TIGIT-ligand binding using antagonistic anti-TIGIT mAbs has shown in vitro potential to restore T-cell function and therapeutic efficacy in murine tumor models when combined with...

journal_title：Molecular cancer therapeutics

authors： Preillon J,Cuende J,Rabolli V,Garnero L,Mercier M,Wald N,Pappalardo A,Denies S,Jamart D,Michaux AC,Pirson R,Pitard V,Bagot M,Prasad S,Houthuys E,Brouwer M,Marillier R,Lambolez F,Marchante JR,Nyawouame F,Carter MJ

更新日期：2021-01-01 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：:Cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacologic inhibitors of these kinases function to inhibit cell-cycle progression and exert other important effects on the tumor and host environment. Because of their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have ...

journal_title：Molecular cancer therapeutics

authors： Roberts PJ,Kumarasamy V,Witkiewicz AK,Knudsen ES

更新日期：2020-08-01 00:00:00

abstract：:Integrin-linked kinase (ILK) was assesed as a therapeutic target in glioblastoma xenograft models through multiple endpoints including treatment related changes in the tumor microenvironment. Glioblastoma cell lines were tested in vitro for sensitivity toward the small-molecule inhibitors QLT0254 and QLT0267. Cell via...

journal_title：Molecular cancer therapeutics

authors： Edwards LA,Woo J,Huxham LA,Verreault M,Dragowska WH,Chiu G,Rajput A,Kyle AH,Kalra J,Yapp D,Yan H,Minchinton AI,Huntsman D,Daynard T,Waterhouse DN,Thiessen B,Dedhar S,Bally MB

更新日期：2008-01-01 00:00:00

abstract：:Endothelins (ETs) are a group of vasoactive peptides (ET-1, ET-2 and ET-3) produced by many cell types that bind to G-protein-linked transmembrane receptors, ET-A receptors (ET-RAs) and ET-B receptors (ET-RBs). These peptides are expressed in several human tumors, including carcinomas of the breast, and have a mitogen...

journal_title：Molecular cancer therapeutics

authors： Grimshaw MJ,Naylor S,Balkwill FR

更新日期：2002-12-01 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：:Tissue transglutaminase 2 belongs to a family of transglutaminase proteins that confers mechanical resistance from proteolysis and stabilizes proteins. Transglutaminase 2 promotes transamidation between glutamine and lysine residues with the formation of covalent linkages between proteins. Transglutaminase 2 also inte...

journal_title：Molecular cancer therapeutics

authors： Yuan L,Choi K,Khosla C,Zheng X,Higashikubo R,Chicoine MR,Rich KM

更新日期：2005-09-01 00:00:00

abstract：:AMAD, an emodin azide methyl anthraquinone derivative, was extracted from the nature giant knotweed rhizome of traditional Chinese herbs. Here, we investigated the anticancer activities and signaling pathways implicated in AMAD-induced apoptosis in human breast cancer cell lines MDA-MB-453 and human lung adenocarcinom...

journal_title：Molecular cancer therapeutics

authors： Yan Y,Su X,Liang Y,Zhang J,Shi C,Lu Y,Gu L,Fu L

更新日期：2008-06-01 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：:The PI3K/AKT/mTOR pathway, which is aberrantly stimulated in many cancer cells, has emerged as a target for therapy. However, mTORC1/S6K also mediates negative feedback loops that attenuate upstream signaling. Suppression of these feedback loops opposes the growth-suppressive effects of mTOR inhibitors and leads to dr...

journal_title：Molecular cancer therapeutics

authors： Soares HP,Ming M,Mellon M,Young SH,Han L,Sinnet-Smith J,Rozengurt E

更新日期：2015-04-01 00:00:00