A randomized phase II study of PX-12, an inhibitor of thioredoxin in patients with advanced cancer of the pancreas following progression after a gemcitabine-containing combination.

PubWeight™: 0.96‹?› | Rank: Top 15%

🔗 View Article (PMID 20461382)

Published in Cancer Chemother Pharmacol on May 12, 2010

Authors

Ramesh K Ramanathan1, James Abbruzzese, Tomislav Dragovich, Lynn Kirkpatrick, Jose M Guillen, Amanda F Baker, Linda A Pestano, Sylvan Green, Daniel D Von Hoff

Author Affiliations

1: Virgina G Piper Cancer Center, TGen, Scottsdale, AZ, 85259, USA. rramanathan@tgen.org

Associated clinical trials:

Study of Gefitinib and Docetaxel as Salvage Therapy in Advanced Pancreatic Carcinoma | NCT00177242

Articles citing this

Fungal antioxidant pathways promote survival against neutrophils during infection. J Clin Invest (2012) 1.37

Inhibition of thioredoxin 1 leads to apoptosis in drug-resistant multiple myeloma. Oncotarget (2015) 0.94

DCPIP (2,6-dichlorophenolindophenol) as a genotype-directed redox chemotherapeutic targeting NQO1*2 breast carcinoma. Free Radic Res (2010) 0.93

APE1/Ref-1 regulates STAT3 transcriptional activity and APE1/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival. PLoS One (2012) 0.90

Nuclear expression of thioredoxin-1 in the invasion front is associated with outcome in patients with gallbladder carcinoma. HPB (Oxford) (2012) 0.88

Thiostrepton is an inducer of oxidative and proteotoxic stress that impairs viability of human melanoma cells but not primary melanocytes. Biochem Pharmacol (2012) 0.88

A phase I trial of PX-12, a small-molecule inhibitor of thioredoxin-1, administered as a 72-hour infusion every 21 days in patients with advanced cancers refractory to standard therapy. Invest New Drugs (2011) 0.84

A phase IB trial of 24-hour intravenous PX-12, a thioredoxin-1 inhibitor, in patients with advanced gastrointestinal cancers. Invest New Drugs (2012) 0.81

Selective inhibition of extracellular thioredoxin by asymmetric disulfides. J Med Chem (2013) 0.80

Thioredoxin-1 inhibitor PX-12 induces human acute myeloid leukemia cell apoptosis and enhances the sensitivity of cells to arsenic trioxide. Int J Clin Exp Pathol (2014) 0.80

Targeting reactive oxygen species in development and progression of pancreatic cancer. Expert Rev Anticancer Ther (2016) 0.77

PX-12 inhibits the growth of hepatocelluar carcinoma by inducing S-phase arrest, ROS-dependent apoptosis and enhances 5-FU cytotoxicity. Am J Transl Res (2015) 0.76

Clinically Evaluated Cancer Drugs Inhibiting Redox Signaling. Antioxid Redox Signal (2016) 0.75

Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation. PLoS One (2016) 0.75

Multiple myeloma cells capacity to decompose H2O2 determines lenalidomide sensitivity. Blood (2016) 0.75

Binding of phenothiazines into allosteric hydrophobic pocket of human thioredoxin 1. Eur Biophys J (2016) 0.75

Articles by these authors

Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell (2012) 7.57

Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med (2009) 7.23

Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol (2010) 6.34

Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol (2003) 4.56

American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays. J Clin Oncol (2004) 4.48

Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res (2011) 4.05

Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther (2007) 3.61

Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res (2002) 2.71

Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J Clin Oncol (2009) 2.69

Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. J Clin Oncol (2009) 2.66

Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol (2006) 2.61

Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res (2002) 2.55

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. J Clin Oncol (2005) 2.53

The cationic porphyrin TMPyP4 down-regulates c-MYC and human telomerase reverse transcriptase expression and inhibits tumor growth in vivo. Mol Cancer Ther (2002) 2.39

Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha. Mol Cancer Ther (2004) 2.32

Stability of phosphoprotein as a biological marker of tumor signaling. Clin Cancer Res (2005) 2.31

Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling. Mol Cancer Ther (2004) 2.25

Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer (2004) 2.19

Automated registration of sequential breath-hold dynamic contrast-enhanced MR images: a comparison of three techniques. Magn Reson Imaging (2011) 2.15

Pharmacokinetics of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors: the role of alpha-1-acid glycoprotein binding. Clin Cancer Res (2011) 2.12

Copy number alterations in pancreatic cancer identify recurrent PAK4 amplification. Cancer Biol Ther (2008) 2.09

Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer (2012) 2.01

Hypoxia inducible factor-1alpha as a cancer drug target. Mol Cancer Ther (2004) 1.92

Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep (2012) 1.91

Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N Engl J Med (2015) 1.75

Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints. Cancer Res (2002) 1.72

PRL phosphatases as potential molecular targets in cancer. Mol Cancer Ther (2005) 1.67

The mitotic serine threonine kinase, Aurora-2, is a potential target for drug development in human pancreatic cancer. Mol Cancer Ther (2004) 1.65

Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer (2011) 1.64

Molecular evidence for increased antitumor activity of gemcitabine by genistein in vitro and in vivo using an orthotopic model of pancreatic cancer. Cancer Res (2005) 1.57

Down-regulation of platelet-derived growth factor-D inhibits cell growth and angiogenesis through inactivation of Notch-1 and nuclear factor-kappaB signaling. Cancer Res (2007) 1.56

The Apnea Positive Pressure Long-term Efficacy Study (APPLES): rationale, design, methods, and procedures. J Clin Sleep Med (2006) 1.52

The Brain Tumor Cooperative Group NIH Trial 87-01: a randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine. Neurosurgery (2002) 1.50

RuleMonkey: software for stochastic simulation of rule-based models. BMC Bioinformatics (2010) 1.49

Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer. J Transl Med (2009) 1.48

Direct tandem mass spectrometry reveals limitations in protein profiling experiments for plasma biomarker discovery. J Proteome Res (2005) 1.45

Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478. Neoplasia (2005) 1.45

Altered decamer and nonamer from an HLA-A0201-restricted epitope of Survivin differentially stimulate T-cell responses in different individuals. Vaccine (2011) 1.43

Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells. Mol Cancer Ther (2006) 1.41

Drug targeting of the c-MYC promoter to repress gene expression via a G-quadruplex silencer element. Semin Oncol (2006) 1.39

The association between obstructive sleep apnea and neurocognitive performance--the Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep (2011) 1.35

Translational therapeutic opportunities in ductal adenocarcinoma of the pancreas. Clin Cancer Res (2012) 1.33

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules. Cancer Chemother Pharmacol (2012) 1.30

Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells. Clin Cancer Res (2009) 1.29

Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitor wortmannin. Org Biomol Chem (2004) 1.27

Identification of human polo-like kinase 1 as a potential therapeutic target in pancreatic cancer. Mol Cancer Ther (2004) 1.24

Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy (2010) 1.24

Targeting Aurora-2 kinase in cancer. Mol Cancer Ther (2003) 1.23

Potentiation of the effect of erlotinib by genistein in pancreatic cancer: the role of Akt and nuclear factor-kappaB. Cancer Res (2006) 1.23

Radiosensitization and stromal imaging response correlates for the HIF-1 inhibitor PX-478 given with or without chemotherapy in pancreatic cancer. Mol Cancer Ther (2010) 1.20

Simulation of large-scale rule-based models. Bioinformatics (2009) 1.18

Synergistic effect between erlotinib and MEK inhibitors in KRAS wild-type human pancreatic cancer cells. Clin Cancer Res (2011) 1.17

Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look. Cancer Discov (2011) 1.17

The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging. Clin Cancer Res (2005) 1.17

Tissue transglutaminase regulates focal adhesion kinase/AKT activation by modulating PTEN expression in pancreatic cancer cells. Clin Cancer Res (2008) 1.15

In vivo molecular pharmacology and antitumor activity of the targeted Akt inhibitor PX-316. Oncol Res (2004) 1.14

Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs. BMC Genomics (2013) 1.13

Tubulin-associated drug targets: Aurora kinases, Polo-like kinases, and others. Semin Oncol (2006) 1.12

Synergistic effects of multiple natural products in pancreatic cancer cells. Life Sci (2008) 1.11

Hepatic resection: the last surgical frontier for colorectal cancer. J Clin Oncol (2005) 1.11

Gene expression profiling-based identification of cell-surface targets for developing multimeric ligands in pancreatic cancer. Mol Cancer Ther (2008) 1.10

A pilot study utilizing multi-omic molecular profiling to find potential targets and select individualized treatments for patients with previously treated metastatic breast cancer. Breast Cancer Res Treat (2014) 1.08

A phase I and pharmacokinetic study of ecteinascidin-743 on a daily x 5 schedule in patients with solid malignancies. Clin Cancer Res (2002) 1.07

Identification of an agent selectively targeting DPC4 (deleted in pancreatic cancer locus 4)-deficient pancreatic cancer cells. Cancer Res (2006) 1.06

Aurora-A over-expression in high-grade PIN lesions and prostate cancer. Prostate (2005) 1.06

A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. Clin Cancer Res (2006) 1.06

Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma: results of a phase II trial. Am J Clin Oncol (2008) 1.05

CK2 inhibitor CX-4945 suppresses DNA repair response triggered by DNA-targeted anticancer drugs and augments efficacy: mechanistic rationale for drug combination therapy. Mol Cancer Ther (2012) 1.05

Role of polyamines in arginine-dependent colon carcinogenesis in Apc(Min) (/+) mice. Mol Carcinog (2006) 1.04

Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer. J Gastrointest Surg (2011) 1.03

The skin and hair as surrogate tissues for measuring the target effect of inhibitors of phosphoinositide-3-kinase signaling. Cancer Chemother Pharmacol (2006) 1.03

Skeletal metastases in pancreatic cancer: a retrospective study and review of the literature. Yale J Biol Med (2009) 1.03

Genetic and nongenetic covariates of pain severity in patients with adenocarcinoma of the pancreas: assessing the influence of cytokine genes. J Pain Symptom Manage (2009) 1.02

Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial. Cancer Chemother Pharmacol (2006) 1.02

Down-regulation of Yes Associated Protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells. PLoS One (2012) 1.02

Response to a third-line mitomycin C (MMC)-based chemotherapy in a patient with metastatic pancreatic adenocarcinoma carrying germline BRCA2 mutation. JOP (2008) 1.02

Tumor-stromal interactions in pancreatic cancer. Crit Rev Oncog (2013) 1.01

A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors. Clin Cancer Res (2012) 1.01

UA62784, a novel inhibitor of centromere protein E kinesin-like protein. Mol Cancer Ther (2009) 1.01

Treatment with HIF-1alpha antagonist PX-478 inhibits progression and spread of orthotopic human small cell lung cancer and lung adenocarcinoma in mice. J Thorac Oncol (2010) 1.00

Detection of in vivo enzyme activity with CatalyCEST MRI. Magn Reson Med (2014) 1.00

Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. Invest New Drugs (2010) 1.00

Identification of thioredoxin-interacting protein 1 as a hypoxia-inducible factor 1alpha-induced gene in pancreatic cancer. Pancreas (2008) 0.99

A historical perspective of anthracycline cardiotoxicity. Heart Fail Clin (2011) 0.99

Overexpression of tumor vascular endothelial growth factor A may portend an increased likelihood of progression in a phase II trial of bevacizumab and erlotinib in resistant ovarian cancer. Clin Cancer Res (2010) 0.99

Bortezomib with or without irinotecan in relapsed or refractory colorectal cancer: results from a randomized phase II study. J Clin Oncol (2008) 0.98

Quiescin sulfhydryl oxidase 1 promotes invasion of pancreatic tumor cells mediated by matrix metalloproteinases. Mol Cancer Res (2011) 0.98

A pilot study using next-generation sequencing in advanced cancers: feasibility and challenges. PLoS One (2013) 0.98

Small interfering RNA-mediated knockdown of PRL phosphatases results in altered Akt phosphorylation and reduced clonogenicity of pancreatic cancer cells. Mol Cancer Ther (2008) 0.97

Adrenocortical carcinoma survival rates correlated to genomic copy number variants. Mol Cancer Ther (2008) 0.96

Management strategies in pancreatic cancer. Am J Health Syst Pharm (2011) 0.96

Paired tumor and normal whole genome sequencing of metastatic olfactory neuroblastoma. PLoS One (2012) 0.95

Lenalidomide: targeted anemia therapy for myelodysplastic syndromes. Cancer Control (2006) 0.95

The impact of concomitant medication use on patient eligibility for phase I cancer clinical trials. J Cancer (2012) 0.94

The antitumor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl disulfide) decreases thioredoxin-1 and VEGF levels in cancer patient plasma. J Lab Clin Med (2006) 0.93