PubMed Journals Articles About "A VX-680 (an Aurora Kinase Inhibitor) Study In Patients With Advanced Cancer" RSS

16:15 EDT 17th October 2018 | BioPortfolio

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Showing "Aurora Kinase Inhibitor Study Patients With Advanced Cancer" PubMed Articles 1–25 of 92,000+

A phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors.

Background Aurora kinase overexpression or amplifications are associated with high proliferation, poor prognosis, and therapeutic resistance in human tumors. AMG 900 is an investigational, oral, selective pan-Aurora kinase inhibitor. Methods This first-in-human trial included dose-escalation and dose-expansion phases ( : NCT00858377). Dose escalation evaluated the safety, tolerability, and pharmacokinetics of AMG 900 in advanced solid tumors and determined the maximum tolerated dose (MTD)...

c-Myc is a major determinant for antitumor activity of Aurora A kinase inhibitor MLN8237 in thyroid cancer.

c-Myc is overexpressed in different types of cancer including thyroid cancer, and is considered undruggable over the decades. There is evidence showing that MLN8237, a kind of Aurora A kinase (AURKA) inhibitor, destabilizes c-Myc proteins in liver cancer cells through disrupting c-Myc/AURKA complex. However, the role of MLN8237 in thyroid cancer remains largely unclear. Our aims were to test therapeutic potential of MLN8237 in thyroid cancer, and to analyze determinant factors affecting the response of thyr...

Polymer Nanovesicle mediated delivery of MLN8237 preferentially inhibits Aurora Kinase A to target RalA and Anchorage-Independent Growth in Breast Cancer Cells.

The small GTPase RalA is a known mediator of anchorage-independent growth in cancers and differentially regulated by adhesion and Aurora Kinase A (AURKA). Inhibiting AURKA hence offers a means of specifically targeting RalA (over RalB) in cancer cells. MLN8237 (alisertib) is a known inhibitor of Aurora Kinases, its specificity for AURKA, however, is compromised by its poor solubility and transport across the cell membrane. A Polymer nanovesicle platform is used for the first time to deliver and differential...

Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in Advanced Nonthyroidal Cancer Patients.

Thyroid dysfunction during tyrosine kinase inhibitor (TKI) cancer treatment is common, but predisposing risk factors have not been determined. Recommendations for monitoring patients treated with one or multiple TKI and in conjunction with other relevant cancer therapies could be improved. The study objective was to assess the risk factors for new thyroid dysfunction in TKI-treated previously euthyroid cancer patients.

Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers.

Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction is recognized as a common adverse effect of treatment, but the importance of incident hypothyroidism during TKI therapy remains unclear. This study analyzed the prognostic significance of hypothyroidism during TKI therapy in cancer patients.

A Phase II Study of Pembrolizumab in EGFR-mutant, PD-L1+, Tyrosine Kinase Inhibitor (TKI) Naïve Patients with Advanced NSCLC.

Despite the significant antitumor activity of pembrolizumab in non-small cell lung cancer (NSCLC), clinical benefit has been less frequently observed in patients whose tumors harbor epidermal growth factor receptor (EGFR) mutations compared to EGFR wild-type patients. Our single center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI na...

Brigatinib in Patients with Alectinib-Refractory ALK-Positive Non-Small Cell Lung Cancer: A Retrospective Study.

The second-generation ALK inhibitor alectinib recently demonstrated superior efficacy compared to the first-generation ALK inhibitor crizotinib in advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), establishing alectinib as the new standard first-line therapy. Brigatinib, another second-generation ALK inhibitor, has demonstrated substantial activity in patients with crizotinib-refractory ALK-positive NSCLC; however, its activity in the alectinib-refractory setting is un...

Structure-based drug design: Synthesis and biological evaluation of quinazolin-4-amine derivatives as selective Aurora A kinase inhibitors.

Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly selective Aurora A inhibitors is difficult because Aurora A and B share high homology and differ only by three residues in their ATP-binding pockets. Through structure-based drug design, we design...

First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13).

PQR309 is an orally bioavailable, balanced pan-phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR) C1 and mTORC2 inhibitor.

Design and synthesis of BPR1K653 derivatives targeting the back pocket of Aurora kinases for selective isoform inhibition.

Twenty five novel chemical analogs of the previously reported Aurora kinase inhibitor BPR1K653 (1-(4-(2-((5-chloro-6-phenylfuro[2,3-d]pyrimidin-4-yl)amino)ethyl)phenyl)-3-(2-((dimethylamino)methyl)phenyl)urea) have been designed, synthesized, and evaluated by Aurora-A and Aurora-B enzymatic kinase activity assays. Similar to BPR1K653, analogs 3b-3h bear alkyl or tertiary amino group at the ortho position of the phenylurea, and showed equal or better inhibition activity for Aurora-B over Aurora-A. Conversely...

EGFR L792H and G796R: Two Novel Mutations Mediating Resistance to the Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Osimertinib.

The third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) osimertinib has been approved in many countries to treat advanced non-small cell lung cancer (NSCLC) in patients with the EGFR T790M mutation. As the development of acquired resistance is inevitable, the mechanisms of such resistance must be urgently clarified.

BPR1J373, a novel multi-targeted kinase inhibitor, effectively suppresses the growth of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is a prototype of KIT-driven cancer. KIT gene mutations are found in approximately 80% of GIST, and most of these mutations occur in exon 9 and exon 11. Imatinib has been successfully used as a first-line treatment for advanced GIST, with a significant improvement in progression-free survival (PFS) and overall survival. However, disease progression may develop due to primary or secondary resistance to imatinib. Sunitinib and regorafenib have been approved as second- and...

Use of apatinib combined with pemetrexed for advanced ovarian cancer: A case report.

Ovarian cancer is the most deadly gynecologic cancer, and the therapy is very difficult. Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. At present, there are few studies or case reports on apatinib treatment for patients with ovarian cancer.

Real-world EGFR testing in patients with stage IIIB/IV non-small-cell lung cancer in North China: A multicenter, non-interventional study.

Before tyrosine kinase inhibitor (TKI) therapy can be administered in patients with advanced non-small cell lung cancer (NSCLC), EGFR mutation testing is required. However, few studies have evaluated the extent of EGFR testing in real-world practice in China.

Real-world anaplastic lymphoma kinase (ALK) rearrangement testing patterns, treatment sequences, and survival of ALK inhibitor-treated patients.

The anaplastic lymphoma kinase (ALK) treatment landscape is crowded following recent ALK inhibitor approvals, and updated information on real-world treatment patterns in advanced non-small-cell lung cancer (aNSCLC) with ALK rearrangement (ALK+) is needed.

Comment on: Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713 patients: Meta-analysis of incidence and risk factors of EGFR-TKI pneumonitis in NSCLC.

Pyrazolo4,3-bpyrimido4,5-e1,4diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR.

Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biol...

First-in-Human Phase I Study of AC0010, a Mutant-Selective EGFR Inhibitor in Non-Small Cell Lung Cancer: Safety, Efficacy, and Potential Mechanism of Resistance.

AC0010 is a mutation-selective, third-generation EGFR tyrosine kinase inhibitor (TKI). This first-in-human phase I trial determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AC0010 in patients with advanced or recurrent NSCLC and acquired resistance to the first-generation EGFR-TKI.

Mutation abundance affects the therapeutic efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma: a retrospective analysis.

To investigate the influence of mutation abundance and sites of epidermal growth factor receptor (EGFR) on therapeutic efficacies of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatments of patients with advanced non-small cell lung carcinoma (NSCLC).

Efficacy, safety and predictive indicators of apatinib after multilines treatment in advanced nonsquamous nonsmall cell lung cancer: Apatinib treatment in nonsquamous NSCLC.

Patients with advanced nonsquamous nonsmall cell lung cancer (NSCLC) who experienced progression with two or more lines chemotherapy have no treatment options that clearly confer a survival benefit. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, apatinib has a certain antitumor effect for various solid tumors. The present study evaluated the efficacy and safety of apatinib in advanced nonsquamous NSCLC as salvage treatment in Chinese real-world practice.

Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2.

Buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus fulvestrant in the BELLE-2 study significantly improved progression-free survival (PFS) in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.

Does the Poly (ADP-Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from 60 Prospectively Treated Patients.

More than 80% of patients with advanced cancer develop weight loss. Because preclinical data suggest poly (ADP-ribose) polymerase (PARP) inhibitors can treat this weight loss, this study was undertaken to explore the PARP inhibitor veliparib for this indication.

Long-term safety and survival with gefitinib in select patients with advanced non-small cell lung cancer: Results from the US IRESSA Clinical Access Program (ICAP).

This is the first report of long-term (>10 years) safety, tolerability, and survival data on patients with non-small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.

Long non-coding RNA taurine-upregulated gene 1 correlates with poor prognosis, induces cell proliferation, and represses cell apoptosis via targeting aurora kinase A in adult acute myeloid leukemia.

This study aimed to investigate the correlation of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) with clinicopathological feature and prognosis, and to explore its effect on cell proliferation and apoptosis as well as the relevant target genes in adult acute myeloid leukemia (AML). LncRNA TUG1 expression was detected in bone marrow samples from 186 AML patients and 62 controls. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor lentivirus vectors were transfected in ...

Brief Report: Increased Hepatotoxicity Associated with Sequential Immune Checkpoint Inhibitor and Crizotinib Therapy in Patients with Non-Small-Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) are standard therapies in advanced non-small-cell lung cancer (NSCLC). While genotype-directed tyrosine kinase inhibitors (TKIs) represent the standard of care for subsets of oncogene-driven NSCLC, patients may receive ICIs during their disease course. The impact of sequential ICI/TKI therapy on the risk of hepatotoxicity has not been described.

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