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

22:23 EST 15th December 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...

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...

A phase I study to assess the safety, tolerability, and pharmacokinetics of CXD101 in patients with advanced cancer.

In the current study, the authors sought to determine the maximum tolerated dose (MTD) of the novel class 1 selective histone deacetylase inhibitor CXD101 in a dose escalation study in patients with advanced solid tumors or recurrent/refractory lymphoma.

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...

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.

Aurora kinase B inhibitor barasertib (AZD1152) inhibits glucose metabolism in gastric cancer cells.

Barasertib is a highly selective Aurora kinase B (AURKB) inhibitor and has been widely applied in a variety of cancer cells to investigate the regulatory function of AURKB. However, the effect of barasertib on glucose metabolism in gastric cancer (GC) remains illustrated. Here, barasertib was identified to effectively reduce glucose uptake and lactate production in GC cells in a dose-dependent and time-dependent manner. The expression levels of GLUT1, LDHA and HK2 were decreased by barasertib treatment of G...

Chromosome instability in tumor cells due to defects in Aurora B mediated error correction at kinetochores.

We characterized a panel of cancer cells and found that they exhibited chromosome instability (CIN) that was associated with high frequencies of aberrant kinetochore:microtubule attachments. Failure to resolve these defective attachments before anaphase onset can lead to missegregation of chromosomes. Aurora B kinase is concentrated at the inner centromere where it contributes to multiple kinetochore functions, one of which is in error-correction. Analysis of several CIN cell lines showed that many aspects ...

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...

A phase I study of single-agent BEZ235 special delivery system sachet in Japanese patients with advanced solid tumors.

BEZ235 is a dual kinase inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin, which are key components of the PI3K pathway. This was an open-label, multicenter, dose-escalation, phase I study of single-agent BEZ235 in Japanese oncology patients to determine the maximum tolerated dose (MTD) of BEZ235 based on dose-limiting toxicities (DLTs).

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.

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...

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.

Inhibition of AURKA Reduces Proliferation and Survival of Gastrointestinal Cancer Cells With Activated KRAS by Preventing Activation of RPS6KB1.

Activation of KRAS signaling and overexpression of the aurora kinase A (AURKA) are often detected in luminal gastrointestinal cancers. We investigated regulation of ribosomal protein S6 kinase B1 (RPS6KB1) by AURKA and the effects of alisertib, an AURKA inhibitor, in mice xenograft tumors grown from human gastrointestinal cancer cells with mutant, activated forms of KRAS.

Low dosage of apatinib monotherapy as rescue treatment in advanced lung squamous cell carcinoma.

Platinum-based doublet chemotherapy and radiotherapy are the standard treatment option in advanced squamous cell carcinoma patients. However, few agents could be selected for subsequent post-second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase, apatinib had been proved in advanced gastric cancer. Here, we showed its efficacy and safety in lung squamous cell carcinoma.

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.

Pyrotinib: First Global Approval.

Pyrotinib is an irreversible dual pan-ErbB receptor tyrosine kinase inhibitor developed for the treatment of HER2-positive advanced solid tumours. Based on positive results in a phase II trial, the drug recently received conditional approval in China for use in combination with capecitabine for the treatment of HER2-positive, advanced or metastatic breast cancer in patients previously treated with anthracycline or taxane chemotherapy. This article summarizes the milestones in the development of pyrotinib l...

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.

An extended phase Ib study of epertinib, an orally active reversible dual EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours.

Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2 inhibitor, has established a recommended daily dose of 800 mg in patients with solid tumours. In this study, we have recruited a larger number of patients to assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour activity.

Prognostic impact of doublecortin-like kinase 1 expression in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

Preoperative chemoradiotherapy (CRT) is a standard therapy for locally advanced rectal cancer; however, the response varies depending on cases. Therefore, CRT-response predictors need to be elucidated. Cancer stem cells (CSCs), comprising a small part of tumors, are associated with tumor progression and recurrence due to their self-renewal and proliferation abilities. Doublecortin-like kinase 1 (DCLK1) is one of the several putative CSC markers; however, the clinical impact of its expression in rectal cance...

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