Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinib.

Abstract:

:Elevated levels of Src kinase expression have been found in a variety of human epithelial cancers. Most notably in colon cancer, elevated Src expression correlates with malignant potential and is also associated with metastatic disease. Dasatinib (BMS-354825) is a novel, orally active, multi-targeted kinase inhibitor that targets Src family kinases and is currently under clinical evaluation for the treatment of solid tumors. However, the effects of dasatinib on epithelial tumors are not fully understood. We show that concentrations of dasatinib that inhibit Src activity do not inhibit proliferation in 10 of 12 colon cancer cells lines. However, inhibition of integrin-dependent adhesion and migration by dasatinib correlated with inhibition of Src activity, suggesting that dasatinib may have anti-invasive or anti-metastatic activity and antiproliferative activity in epithelial tumors. Using phospho-specific antibodies, we show that inhibition of Src activity in colon cancer cell lines correlates with reduced phosphorylation of focal adhesion kinase and paxillin on specific Src-dependent phosphorylation sites. We have validated the use of phospho-specific antibodies against Src Tyr(419) and paxillin Tyr(118) as biomarkers of dasatinib activity in vivo. Colon carcinoma-bearing mice treated with dasatinib showed a decrease in both phospho-Src Tyr(419) and phospho-paxillin Tyr(118) in peripheral blood mononuclear cells, which correlated with inhibition of Src activity in the colon tumors. Thus, peripheral blood mononuclear cells may provide a useful surrogate tissue for biomarker studies with dasatinib using inhibition of Src Tyr(419) and paxillin Tyr(118) phosphorylation as read-outs of Src activity.

journal_name

Mol Cancer Ther

authors

Serrels A,Macpherson IR,Evans TR,Lee FY,Clark EA,Sansom OJ,Ashton GH,Frame MC,Brunton VG

doi

10.1158/1535-7163.MCT-06-0382

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

3014-22

issue

12

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-06-0382

journal_volume

5

pub_type

杂志文章
  • ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain.

    abstract::Epidermal growth factor receptor (EGFR) vIII is a mutated EGFR that is frequently overexpressed in glioblastomas and implicated in response to receptor tyrosine kinase inhibitors. In this study, we investigate the effect of ZD6474 (ZACTIMA, vandetanib), a dual inhibitor for vascular endothelial growth factor receptor ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-0953

    authors: Yiin JJ,Hu B,Schornack PA,Sengar RS,Liu KW,Feng H,Lieberman FS,Chiou SH,Sarkaria JN,Wiener EC,Ma HI,Cheng SY

    更新日期:2010-04-01 00:00:00

  • LncRNA CCAT1 Promotes Prostate Cancer Cell Proliferation by Interacting with DDX5 and MIR-28-5P.

    abstract::Accumulated evidence indicates that CCAT1 functions as an oncogene in the progression of a variety of tumors. However, little is known as to how CCAT1 impacts tumorigenesis in human prostate cancer. In this study, we found from The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center database that CCAT1 is h...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-19-0095

    authors: You Z,Liu C,Wang C,Ling Z,Wang Y,Wang Y,Zhang M,Chen S,Xu B,Guan H,Chen M

    更新日期:2019-12-01 00:00:00

  • E7080 suppresses hematogenous multiple organ metastases of lung cancer cells with nonmutated epidermal growth factor receptor.

    abstract::While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors improve the prognosis of patients with EGFR mutant lung cancer, the prognosis of patients with nonmutant EGFR lung cancer, especially those with metastases, is still extremely poor. We have assessed the therapeutic efficacy of E7080, an orally av...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-10-0707

    authors: Ogino H,Hanibuchi M,Kakiuchi S,Trung VT,Goto H,Ikuta K,Yamada T,Uehara H,Tsuruoka A,Uenaka T,Wang W,Li Q,Takeuchi S,Yano S,Nishioka Y,Sone S

    更新日期:2011-07-01 00:00:00

  • Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics.

    abstract::The extracellular pH of tumor tissue is significantly lower than the extracellular pH of normal tissue, whereas the intracellular pH of both tissues is similar. In principle, extracellular acidity may be expected to enhance the intracellular uptake and cytotoxicity of weak acid chemotherapeutics that are membrane perm...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-06-0024

    authors: Gerweck LE,Vijayappa S,Kozin S

    更新日期:2006-05-01 00:00:00

  • Antitumor activity and immune response induction of a dual agonist of Toll-like receptors 7 and 8.

    abstract::Viral and synthetic single-stranded RNAs are the ligands for Toll-like receptors 7 and 8 (TLR7 and TLR8). We have reported a novel class of synthetic oligoribonucleotides, referred to as stabilized immune-modulatory RNA compounds, which act as agonists of TLR7, TLR8, or both TLR7 and TLR8 depending on the sequence com...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-1198

    authors: Wang D,Precopio M,Lan T,Yu D,Tang JX,Kandimalla ER,Agrawal S

    更新日期:2010-06-01 00:00:00

  • Targeting of β-Catenin Reverses Radioresistance of Cervical Cancer with the PIK3CA-E545K Mutation.

    abstract::This study aims to explore whether E545K, the most common hotspot mutation of PIK3CA in cervical cancer, confers radioresistance to cervical cancer cells, to demonstrate the underling mechanism, and to develop the effective targets. SiHa and MS751 cells with PIK3CA-WT and PIK3CA-E545K were established by lentiviral tr...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-19-0309

    authors: Jiang W,Wu Y,He T,Zhu H,Ke G,Xiang L,Yang H

    更新日期:2020-02-01 00:00:00

  • A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model.

    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

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-05-0313

    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

  • z-Guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo.

    abstract::Our previous studies have shown that z-guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, inhibits the growth of human prostate cancer cells by causing apoptosis. We now report a novel response to z-guggulsterone involving the inhibition of angiogenesis in vitro and in vivo. The z-guggu...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-07-0491

    authors: Xiao D,Singh SV

    更新日期:2008-01-01 00:00:00

  • Combinatorial Treatment with mTOR Inhibitors and Streptozotocin Leads to Synergistic In Vitro and In Vivo Antitumor Effects in Insulinoma Cells.

    abstract::Streptozotocin-based chemotherapy is the first-line chemotherapy recommended for advanced pancreatic neuroendocrine tumors (pNETs), whereas targeted therapies, including mTOR inhibitors, are available in second-line treatment. Unfortunately, objective response rates to both treatments are limited. Because mTOR pathway...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0325

    authors: Bollard J,Patte C,Massoma P,Goddard I,Gadot N,Benslama N,Hervieu V,Ferraro-Peyret C,Cordier-Bussat M,Scoazec JY,Roche C,Walter T,Vercherat C

    更新日期:2018-01-01 00:00:00

  • Therapeutic Potential of Focal Adhesion Kinase Inhibition in Small Cell Lung Cancer.

    abstract::Small cell lung cancer (SCLC) has a poor prognosis. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase regulating cell proliferation, survival, migration, and invasion, which is overexpressed and/or activated in several cancers, including SCLC. We wanted to determine whether FAK contributes to SCLC aggressi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-18-0328

    authors: Aboubakar Nana F,Lecocq M,Ladjemi MZ,Detry B,Dupasquier S,Feron O,Massion PP,Sibille Y,Pilette C,Ocak S

    更新日期:2019-01-01 00:00:00

  • The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents.

    abstract::p53 is a critical tumor suppressor and is the most frequently inactivated gene in human cancer. Inhibition of the interaction of p53 with its negative regulator MDM2 represents a promising clinical strategy to treat p53 wild-type tumors. AMG 232 is a potential best-in-class inhibitor of the MDM2-p53 interaction and is...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-14-0710

    authors: Canon J,Osgood T,Olson SH,Saiki AY,Robertson R,Yu D,Eksterowicz J,Ye Q,Jin L,Chen A,Zhou J,Cordover D,Kaufman S,Kendall R,Oliner JD,Coxon A,Radinsky R

    更新日期:2015-03-01 00:00:00

  • Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells.

    abstract::Dietary phytochemicals exhibit chemopreventive potential in vivo through persistent low-dose exposures, whereas mechanistic in vitro studies with these agents generally use a high-dose single treatment. Because the latter approach is not representative of an in vivo steady state, we investigated antitumor activity of ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-07-0117

    authors: Moiseeva EP,Almeida GM,Jones GD,Manson MM

    更新日期:2007-11-01 00:00:00

  • Circulating Tumor Cells In Advanced Cervical Cancer: NRG Oncology-Gynecologic Oncology Group Study 240 (NCT 00803062).

    abstract::To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-20-0276

    authors: Tewari KS,Sill MW,Monk BJ,Penson RT,Moore DH,Lankes HA,Ramondetta LM,Landrum LM,Randall LM,Oaknin A,Leitao MM,Eisenhauer EL,DiSilvestro P,Van Le L,Pearl ML,Burke JJ,Salani R,Richardson DL,Michael HE,Kindelberger DW

    更新日期:2020-08-26 00:00:00

  • Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through both Tumor-Extrinsic and -Intrinsic Activities.

    abstract::Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-16-0337

    authors: Talbert EE,Yang J,Mace TA,Farren MR,Farris AB,Young GS,Elnaggar O,Che Z,Timmers CD,Rajasekera P,Maskarinec JM,Bloomston M,Bekaii-Saab T,Guttridge DC,Lesinski GB

    更新日期:2017-02-01 00:00:00

  • Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of small cell lung cancer cells through the downregulation of the NF-κB activity.

    abstract::Notch signaling regulates cell-fate decisions during development and postnatal life. Little is known, however, about the role of Delta-like-4 (Dll4)-Notch signaling between cancer cells, or how this signaling affects cancer metastasis. We, therefore, assessed the role of Dll4-Notch signaling in cancer metastasis. We g...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-12-0640

    authors: Kuramoto T,Goto H,Mitsuhashi A,Tabata S,Ogawa H,Uehara H,Saijo A,Kakiuchi S,Maekawa Y,Yasutomo K,Hanibuchi M,Akiyama S,Sone S,Nishioka Y

    更新日期:2012-12-01 00:00:00

  • Inhibition of insulin-like growth factor-binding protein-3 signaling through sphingosine kinase-1 sensitizes triple-negative breast cancer cells to EGF receptor blockade.

    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

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-13-0367

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

    更新日期:2014-02-01 00:00:00

  • Clinicopathological and Functional Significance of RECQL1 Helicase in Sporadic Breast Cancers.

    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

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-16-0290

    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

  • Therapeutic potential of antisense oligodeoxynucleotides to down-regulate thymidylate synthase in mesothelioma.

    abstract::Malignant mesothelioma is an aggressive tumor of the serosal surfaces of the lungs, heart, and abdomen. Survival rates are poor and effective treatments are not available. However, recent therapeutic regimens targeting thymidylate synthase (TS) in malignant mesothelioma patients have shown promise. We have reported th...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-06-0073

    authors: Flynn J,Berg RW,Wong T,van Aken M,Vincent MD,Fukushima M,Koropatnick J

    更新日期:2006-06-01 00:00:00

  • 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors.

    abstract::There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-pa...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-15-0598

    authors: Onion D,Argent RH,Reece-Smith AM,Craze ML,Pineda RG,Clarke PA,Ratan HL,Parsons SL,Lobo DN,Duffy JP,Atherton JC,McKenzie AJ,Kumari R,King P,Hall BM,Grabowska AM

    更新日期:2016-04-01 00:00:00

  • Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI-Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation.

    abstract::Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-16-0313

    authors: Yamaoka T,Ohmori T,Ohba M,Arata S,Kishino Y,Murata Y,Kusumoto S,Ishida H,Shirai T,Hirose T,Ohnishi T,Sasaki Y

    更新日期:2016-12-01 00:00:00

  • 1,25-dihydroxyvitamin D3 enhances the apoptotic activity of MDM2 antagonist nutlin-3a in acute myeloid leukemia cells expressing wild-type p53.

    abstract::The tumor suppressor p53 is often referred to as "the guardian of the genome" because of its central role in the cellular response to oncogenic stress and prevention of tumor development. Mutations of p53 in acute myeloid leukemia (AML) are rare but resistance to chemotherapy has been reported because of the deregulat...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-1036

    authors: Thompson T,Andreeff M,Studzinski GP,Vassilev LT

    更新日期:2010-05-01 00:00:00

  • Growth inhibition of human cancer cells by 5-aza-2'-deoxycytidine does not correlate with its effects on INK4a/ARF expression or initial promoter methylation status.

    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

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0926

    authors: Xiong J,Epstein RJ

    更新日期:2009-04-01 00:00:00

  • A Spatio-Temporal Model of Macrophage-Mediated Drug Resistance in Glioma Immunotherapy.

    abstract::The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0634

    authors: Zheng Y,Bao J,Zhao Q,Zhou T,Sun X

    更新日期:2018-04-01 00:00:00

  • Antitumor activity of the MEK inhibitor TAK-733 against melanoma cell lines and patient-derived tumor explants.

    abstract::The goal of this study was to investigate the activity of the selective MEK1/2 inhibitor TAK-733 in both melanoma cell lines and patient-derived melanoma xenograft models. In vitro cell proliferation assays using the sulforhodamine B assay were conducted to determine TAK-733 potency and melanoma responsiveness. In viv...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-13-1012

    authors: Micel LN,Tentler JJ,Tan AC,Selby HM,Brunkow KL,Robertson KM,Davis SL,Klauck PJ,Pitts TM,Gangolli E,Fabrey R,O'Connell SM,Vincent PW,Eckhardt SG

    更新日期:2015-02-01 00:00:00

  • Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice.

    abstract::Mis-expression of microRNAs (miRNA) is widespread in human cancers, including in pancreatic cancer. Aberrations of miRNA include overexpression of oncogenic miRs (Onco-miRs) or downregulation of so-called tumor suppressor TSG-miRs. Restitution of TSG-miRs in cancer cells through systemic delivery is a promising avenue...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-11-0152

    authors: Pramanik D,Campbell NR,Karikari C,Chivukula R,Kent OA,Mendell JT,Maitra A

    更新日期:2011-08-01 00:00:00

  • Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by alpha-lactalbumin promoter.

    abstract::The breast-specific antigen alpha-lactalbumin is expressed in >60% of breast cancer tissues. To evaluate the effect of gene therapy for breast cancer by controlling adenovirus replication with human alpha-lactalbumin promoter, we investigated the activity of a 762-bp human alpha-lactalbumin promoter. Alpha-lactalbumin...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-05-0167

    authors: Li X,Zhang J,Gao H,Vieth E,Bae KH,Zhang YP,Lee SJ,Raikwar S,Gardner TA,Hutchins GD,VanderPutten D,Kao C,Jeng MH

    更新日期:2005-12-01 00:00:00

  • HER2 as therapeutic target for overcoming ATP-binding cassette transporter-mediated chemoresistance in small cell lung cancer.

    abstract::Small cell lung cancer (SCLC) easily acquires multidrug resistance after successful initial therapy. Overexpression of ATP-binding cassette (ABC) transporters is important for the multidrug resistance. Among them, ABCB1 and ABCG2 are known to be upregulated in chemoresistant SCLC cells. We found that human epidermal g...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-11-0884

    authors: Minami T,Kijima T,Otani Y,Kohmo S,Takahashi R,Nagatomo I,Hirata H,Suzuki M,Inoue K,Takeda Y,Kida H,Tachibana I,Kumanogoh A

    更新日期:2012-04-01 00:00:00

  • D,L-Sulforaphane causes transcriptional repression of androgen receptor in human prostate cancer cells.

    abstract::D,L-Sulforaphane (SFN), a synthetic analogue of cruciferous vegetable-derived L-isomer, inhibits the growth of human prostate cancer cells in culture and in vivo and retards cancer development in a transgenic mouse model of prostate cancer. We now show that SFN treatment causes transcriptional repression of androgen r...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-0104

    authors: Kim SH,Singh SV

    更新日期:2009-07-01 00:00:00

  • Inhibition of Nucleotide Synthesis Targets Brain Tumor Stem Cells in a Subset of Glioblastoma.

    abstract::Inhibition of both the de novo (DNP) and salvage (NSP) pathways of nucleoside synthesis has been demonstrated to impair leukemia cells. We endeavored to determine whether this approach would be efficacious in glioblastoma. To diminish nucleoside biosynthesis, we utilized compound DI-39, which selectively targets NSP, ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-15-0982

    authors: Laks DR,Ta L,Crisman TJ,Gao F,Coppola G,Radu CG,Nathanson DA,Kornblum HI

    更新日期:2016-06-01 00:00:00

  • Combination drug scheduling defines a "window of opportunity" for chemopotentiation of gemcitabine by an orally bioavailable, selective ChK1 inhibitor, GNE-900.

    abstract::Checkpoint kinase 1 (ChK1) is a serine/threonine kinase that functions as a central mediator of the intra-S and G2-M cell-cycle checkpoints. Following DNA damage or replication stress, ChK1-mediated phosphorylation of downstream effectors delays cell-cycle progression so that the damaged genome can be repaired. As a t...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-12-1218

    authors: Blackwood E,Epler J,Yen I,Flagella M,O'Brien T,Evangelista M,Schmidt S,Xiao Y,Choi J,Kowanetz K,Ramiscal J,Wong K,Jakubiak D,Yee S,Cain G,Gazzard L,Williams K,Halladay J,Jackson PK,Malek S

    更新日期:2013-10-01 00:00:00