Activation of IL-6R/JAK1/STAT3 signaling induces de novo resistance to irreversible EGFR inhibitors in non-small cell lung cancer with T790M resistance mutation.

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：:Targeting of epigenetic regulators as the chromatin remodeler SWI/SNF is proving to be a promising therapeutic strategy for individualized treatment of cancer patients. Here, we tested whether targeting one of the two mutually exclusive subdomains of the SWI/SNF complex BRM/SMARCA2 can sensitize specifically non-small...

journal_title：Molecular cancer therapeutics

authors： Zernickel E,Sak A,Riaz A,Klein D,Groneberg M,Stuschke M

更新日期：2019-03-01 00:00:00

abstract：:Most patients with late-stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, making it an attractive therapeutic...

journal_title：Molecular cancer therapeutics

authors： Iavarone C,Zervantonakis IK,Selfors LM,Palakurthi S,Liu JF,Drapkin R,Matulonis UA,Hallberg D,Velculescu VE,Leverson JD,Sampath D,Mills GB,Brugge JS

更新日期：2019-03-01 00:00:00

abstract：:Hepatocellular carcinoma (HCC) can arise from chronic inflammation due to viral infection, organ damage, drug toxicity, or alcohol abuse. Moreover, gene desensitization via aberrant CpG island methylation is a frequent epigenetic defect in HCC. However, the details of how inflammation is linked with epigenetic-mediate...

journal_title：Molecular cancer therapeutics

authors： Li CF,Tsai HH,Ko CY,Pan YC,Yen CJ,Lai HY,Yuh CH,Wu WC,Wang JM

更新日期：2015-11-01 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：: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：:Recent studies have shown that naturally occurring compounds can enhance the efficacy of chemotherapeutic drugs. The objectives of this study were to investigate the molecular mechanisms by which diallyl trisulfide (DATS) enhanced the therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand (TR...

journal_title：Molecular cancer therapeutics

authors： Shankar S,Chen Q,Ganapathy S,Singh KP,Srivastava RK

更新日期：2008-08-01 00:00:00

abstract：:Chemoresistance of ovarian carcinoma has been associated previously to the absence of Bcl-x(L) expression downregulation in response to cisplatin. Among BH3-mimetic molecules constituting promising anticancer agents able to inhibit the activity of antiapoptotic Bcl-2 family proteins, we evaluated the effect of one of ...

journal_title：Molecular cancer therapeutics

authors： Simonin K,Brotin E,Dufort S,Dutoit S,Goux D,N'diaye M,Denoyelle C,Gauduchon P,Poulain L

更新日期：2009-11-01 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：: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：:The MET receptor tyrosine kinase, the receptor for hepatocyte growth factor (HGF), has been implicated in cancer growth, invasion, migration, angiogenesis, and metastasis in a broad variety of human cancers, including human hepatocellular carcinoma (HCC). Recently, MET was suggested to be a potential target for the pe...

journal_title：Molecular cancer therapeutics

authors： Jo JC,Choi EK,Shin JS,Moon JH,Hong SW,Lee HR,Kim SM,Jung SA,Lee DH,Jung SH,Lee SH,Kim JE,Kim KP,Hong YS,Suh YA,Jang SJ,Choi EK,Lee JS,Jin DH,Kim TW

更新日期：2015-11-01 00:00:00

abstract：:DNA methylation, histone modifications, and nucleosomal occupancy collaborate to cause silencing of tumor-related genes in cancer. The development of drugs that target these processes is therefore important for cancer therapy. Inhibitors of DNA methylation and histone deacetylation have been approved by the Food and D...

journal_title：Molecular cancer therapeutics

authors： Miranda TB,Cortez CC,Yoo CB,Liang G,Abe M,Kelly TK,Marquez VE,Jones PA

更新日期：2009-06-01 00:00:00

abstract：:One hallmark of cancer cells is their adaptation to rely upon an altered metabolic scheme that includes changes in the glycolytic pathway, known as the Warburg effect, and elevated glutamine metabolism. Glutaminase, a mitochondrial enzyme, plays a key role in the metabolism of glutamine in cancer cells, and its inhibi...

journal_title：Molecular cancer therapeutics

authors： Katt WP,Ramachandran S,Erickson JW,Cerione RA

更新日期：2012-06-01 00:00:00

abstract：:Several studies have identified silibinin as an anticarcinogenic agent. Recently, we showed that silibinin inhibits cell growth via G1 arrest, leading to differentiation of androgen-dependent human prostate carcinoma LNCaP cells (X. Zi and R. Agarwal, Proc. Natl. Acad. Sci. USA, 96: 7490-7495,1999). Here, we extend th...

journal_title：Molecular cancer therapeutics

authors： Tyagi A,Agarwal C,Agarwal R

更新日期：2002-05-01 00:00:00

abstract：:Protein ubiquitination is important for cell signaling, DNA repair, and proteasomal degradation, and it is not surprising that alterations in ubiquitination occur frequently in cancer. Ubiquitin-conjugating enzymes (E2) mediate ubiquitination by selective interactions with ubiquitin-activating (E1) and ubiquitin ligas...

journal_title：Molecular cancer therapeutics

authors： Sanders MA,Brahemi G,Nangia-Makker P,Balan V,Morelli M,Kothayer H,Westwell AD,Shekhar MPV

更新日期：2013-04-01 00:00:00

abstract：:In the current study, we examined a panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib...

journal_title：Molecular cancer therapeutics

authors： Sarkaria JN,Yang L,Grogan PT,Kitange GJ,Carlson BL,Schroeder MA,Galanis E,Giannini C,Wu W,Dinca EB,James CD

更新日期：2007-03-01 00:00:00

abstract：:Expression of the proto-oncogene Bcl-2 is associated with tumor progression. Bcl-2's broad expression in tumors, coupled with its role in resistance to chemotherapy and radiation therapy-induced apoptosis, makes it a rational target for anticancer therapy. Antisense Bcl-2 oligodeoxynucleotide (ODN) reagents have been ...

journal_title：Molecular cancer therapeutics

authors： Anai S,Goodison S,Shiverick K,Hirao Y,Brown BD,Rosser CJ

更新日期：2007-01-01 00:00:00

abstract：:Plasminogen activator inhibitor-1 (PAI-1) is an important endogenous inhibitor of urokinase-type plasminogen activator. Its action in tumor angiogenesis is complicated, varying with experimental setting and its cellular origin. To further understand the mechanism of the effect of PAI-1 on tumor angiogenesis, especiall...

journal_title：Molecular cancer therapeutics

authors： Chen SC,Henry DO,Reczek PR,Wong MK

更新日期：2008-05-01 00:00:00

abstract：:Gefitinib (Iressa, ZD1839), a quinazoline tyrosine kinase inhibitor that targets the epidermal growth factor receptor (EGFR), is approved for patients with advanced non-small cell lung cancer (NSCLC) in several countries including Japan. However, the mechanism of drug sensitivity to gefitinib is not fully understood. ...

journal_title：Molecular cancer therapeutics

authors： Ono M,Hirata A,Kometani T,Miyagawa M,Ueda S,Kinoshita H,Fujii T,Kuwano M

更新日期：2004-04-01 00:00:00

abstract：:Constitutively activated STAT3 and STAT5 are expressed in a wide variety of human malignancies including solid and hematopoietic cancers and often correlate with a poor prognosis and resistance to multiple therapies. Given the well established role of STAT3 in tumorigenesis, inhibition of Janus-activated kinase 2 (JAK...

journal_title：Molecular cancer therapeutics

authors： Seavey MM,Lu LD,Stump KL,Wallace NH,Hockeimer W,O'Kane TM,Ruggeri BA,Dobrzanski P

更新日期：2012-04-01 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：: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

abstract：:Hsp90 is widely overexpressed in cancer cells and believed to be essential for the maintenance of malignant phenotypes. Targeting Hsp90 by small molecules has shown promise in solid and hematologic malignancies, which likely involves degradation of client oncoproteins in a cell-type-specific manner. In this study, we ...

journal_title：Molecular cancer therapeutics

authors： He K,Zheng X,Zhang L,Yu J

更新日期：2013-11-01 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：: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：:Several studies have evaluated the efficacy of using human oncolytic adenovirus (OAdv)-loaded mesenchymal stem cells (MSC) for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow-mesenchymal stem cells infected with the OAdv ICOVIR-5, for treatment of patients wit...

journal_title：Molecular cancer therapeutics

authors： Moreno R,Fajardo CA,Farrera-Sal M,Perisé-Barrios AJ,Morales-Molina A,Al-Zaher AA,García-Castro J,Alemany R

更新日期：2019-01-01 00:00:00

abstract：:There is an urgent need for the development of novel therapies to treat pancreatic cancer, which is among the most lethal of all cancers. KRAS-activating mutations, which are found in more than 90% of pancreatic adenocarcinomas, drive tumor dependency on the Ras/MAPK and Akt signaling pathways. Radiation is currently ...

journal_title：Molecular cancer therapeutics

authors： Williams TM,Flecha AR,Keller P,Ram A,Karnak D,Galbán S,Galbán CJ,Ross BD,Lawrence TS,Rehemtulla A,Sebolt-Leopold J

更新日期：2012-05-01 00:00:00

abstract：:Previous work has shown that cisplatin (CDDP) becomes concentrated in lysosomes, and that acquired resistance to CDDP is associated with abnormalities of protein trafficking and secretion. The lysosomal compartment in CDDP-sensitive 2008 human ovarian carcinoma cells was compared with that in CDDP-resistant 2008/C13*5...

journal_title：Molecular cancer therapeutics

authors： Safaei R,Larson BJ,Cheng TC,Gibson MA,Otani S,Naerdemann W,Howell SB

更新日期：2005-10-01 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

abstract：:The cytotoxicity of 5-aza-2'-deoxycytidine (DAC) has been linked to demethylation of the INK4a/ARF tumor suppressor gene locus in various cell systems, but the causality of this association remains unproven. To test this assumption, we have examined the effects of DAC in two human cancer cell lines of differing INK4a/...

journal_title：Molecular cancer therapeutics

authors： Xiong J,Epstein RJ

更新日期：2009-04-01 00:00:00