• This communication describes the discovery of a novel series of Aurora kinase inhibitors. (rcsb.org)
  • Finally the last section will be devoted to a new class of compounds that are able to inhibit both mTOR complexes and the new dual inhibitors that are also adding activity against the phosphatydilinositol-3-kinase (PI3K) a key component of the main opinions loop involved in this pathway. (biomasswars.com)
  • This observation has provided rationale for combining several ongoing phase I clinical trials combining mTOR PI3K or AKT inhibitors with MAP/ERK kinase (MEK) inhibitors. (biomasswars.com)
  • Considering these preclinical and clinical results in conjunction the combination of PI3K or second generation mTOR inhibitors with MEK inhibitors warrants further clinical validation. (biomasswars.com)
  • In addition, Vertex could earn additional milestone payments for the development of Aurora kinase inhibitors outside the area of oncology. (vrtx.com)
  • Aurora kinases are implicated in the onset and progression of many different human cancers, and novel Aurora kinase inhibitors such as VX-680 have the potential to play an important future role in the treatment and management of a wide range of tumor types. (vrtx.com)
  • We are pleased to enter this collaboration with Merck, which shares our vision of Aurora kinase inhibitors as a class of drugs that may have the potential to transform the future of cancer treatment," said Joshua Boger, Ph.D., Chairman and CEO of Vertex. (vrtx.com)
  • Applying "drug target constellation" (DTECT) mapping, we further show that protein levels of TTF1 and cMYC predict response to targeted therapies including aurora kinase, Bcl2, and HSP90 inhibitors. (oncotarget.com)
  • He has conducted/participated a number of clinical trials with immune checkpoint inhibitors and targeted therapy agents. (ucsf.edu)
  • A unique collection of 408 kinase inhibitors for high throughput screening (HTS) and high content screening (HCS). (abmole.com)
  • The findings, published June 6 in the Journal of the National Cancer Institute, could one day help physicians decide which lung cancer patients to treat with drugs known collectively as EGF receptor tyrosine kinase inhibitors, a step forward in the era of personalized medicine. (eurekalert.org)
  • In the case of the EGF receptor tyrosine kinase inhibitors (TKIs) gefitinib (Iressa) and erlotinib (Tarceva), studies have demonstrated a survival benefit for 30 to 40 percent of lung cancer patients, but there has been no method for identifying these patients prior to treatment, Carbone said. (eurekalert.org)
  • Clinical studies have shown that subsets of patients with cancer achieve a significant benefit from Aurora kinase inhibitors, suggesting an urgent need to identify biomarkers for predicting drug response. (figshare.com)
  • Here, we show that CHD1 promotes the susceptibility of prostate cancer cells to inhibitors targeting Aurora kinases, while depletion of CHD1 impairs their efficacy in vitro and in vivo. (figshare.com)
  • Pan-cancer drug sensitivity analyses revealed that high expression of CHD1 was associated with increased sensitivity to Aurora kinase A (AURKA) inhibitors. (figshare.com)
  • Pharmacological response data for targeted inhibitors of SRC, WNT, GSK3b, aurora kinase, PI3 kinase, and mTOR, showed significant differences in sensitivity across cell lines assigned to different subtypes. (tudelft.nl)
  • Mount Sinai researchers have developed a novel method to identify aggressive early-stage lung cancers and target drugs known as aurora kinase inhibitors to tumors that are especially likely to respond. (bio-itworld.com)
  • The Mount Sinai team used a genomics network model to measure tumor invasiveness-distinguishing aggressive tumors from so-called "indolent" ones, which often cannot be told apart via chest CT scan-and identify those that will respond to aurora kinase inhibitors, molecules that can inhibit gene signature regulators. (bio-itworld.com)
  • They identified and tested aurora kinase inhibitors, including AMG900, as an effective treatment to intercept lung cancer progression in the models. (bio-itworld.com)
  • Here, we explore why some Aurora kinase inhibitors cause preferential neutropenia. (bvsalud.org)
  • TKIs, aurora kinase inhibitors and homoharringtonine. (rockstarsagainstliveearth.com)
  • Therapy with tyrosine kinase inhibitors (TKIs) has changed the natural history of CML, which has gone from a potentially fatal disorder to one that can be easily controlled [8]. (rockstarsagainstliveearth.com)
  • 1. Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in pre-clinical models of aggressive lymphomas. (mutalig.eu)
  • 4. Novel HDAC inhibitors exhibit pre-clinical efficacy in lymphoma models and point to the importance of CDKN1A expression levels in mediating their anti-tumor response. (mutalig.eu)
  • ORIC discovered novel, potent, orally bioavailable small molecule inhibitors of PLK4 that are highly selective, including against the closely related aurora kinases and PLK1-3. (oricpharma.com)
  • Pfizer) plus Everolimus are underway (35 36 Furthermore preclinical data have shown that mTORC1 inhibition results in a hyperactivation of the PI3K pathway and simultaneous increase of the signaling through the mitogen-activated protein kinase kinase (MAPK) pathway (37) thus proving the presence of another opinions loop that connect the PI3K-AKT-mTOR with the MAPK pathway. (biomasswars.com)
  • By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing gene expression datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibition is caused by early developmental changes in ATP-binding cassette (ABC) transporter expression. (bvsalud.org)
  • In a phase Ib trial reported in the Journal of Clinical Oncology , D. Ross Camidge, MD, PhD , and colleagues found that the combination of telisotuzumab vedotin and erlotinib showed activity in c-Met protein-expressing advanced non-small cell lung cancer (NSCLC), including those with an EGFR mutation and prior EGFR tyrosine kinase inhibitor treatment. (ascopost.com)
  • later enrollment was restricted to patients who also had an EGFR -activating mutation and disease progression on a prior EGFR tyrosine kinase inhibitor. (ascopost.com)
  • The translocation occurs in a primitive hematopoietic stem cell and the gene encodes a fusion protein (Bcr-Abl) that has deregulated tyrosine kinase (TK) activity and activates intracellular pathways that lead to increased cellular proliferation, resistance to apoptosis and genetic instability [1,3]. (rockstarsagainstliveearth.com)
  • Tumor-related studies have shown the clinical application and research prospects of this gene, suggesting that it might play the important role in the treatment of tumors. (hindawi.com)
  • These tumors are particularly noted for extensive heterogeneity in clinical behaviour, ranging from spontaneous regression to aggressive clinical course and death from disease. (biomedcentral.com)
  • Selinexor, a small molecule that inhibits nuclear export protein XPO1, has demonstrated efficacy in solid tumors and hematologic malignancies with the evidence of clinical activity in sarcoma as a single agent. (aacrjournals.org)
  • In Merck, we have a partner that is a global leader in the development and commercialization of innovative medicines, and one with the breadth of capabilities and resources that we expect to be required to establish the clinical benefit of an Aurora kinase inhibitor across a spectrum of solid tumors and hematologic cancers. (vrtx.com)
  • A genomic network model is used to identify aurora kinase inhibitor-sensitive lung tumors, new Illumina Accelerator start-ups are announced, AI algorithms are being used to improve prostate cancer identification and treatment, and a blood-based DNA methylation test can detect liver cancer. (bio-itworld.com)
  • Gaining insight into the heterogeneity of nanoparticle drug distribution within tumors would improve both design and clinical translation of nanomedicines. (thno.org)
  • This was used to assess the nanomedicine AZD2811 in animals bearing three different pre-clinical PDX tumors. (thno.org)
  • These results demonstrated that H2AK119Ub1 and H3K27Me3 cooperate in tumors and are associated with the clinical prognosis in combinatorial patterns. (oncotarget.com)
  • SCARA5 expression is significantly downregulated in various tumor tissues including liver cancer (LC), rectal cancer, and glioblastoma [ 15 , 16 ] and might affect cell proliferation and invasion abilities by the focal adhesion kinase (FAK) signaling pathway and epithelial-mesenchymal transition (EMT) [ 5 , 17 - 20 ]. (hindawi.com)
  • There's a real clinical need to identify which patients will benefit from targeted therapies," said David Carbone, M.D., Ph.D., Harold L. Moses Professor of Cancer Research at Vanderbilt-Ingram and the senior author of the study. (eurekalert.org)
  • These observations demonstrate that CHD1 plays an important role in modulating Aurora kinases and drug sensitivities, providing new insights into biomarker-driven therapies targeting Aurora kinases for future clinical studies. (figshare.com)
  • To tailor CRC treatment, it is essential to first model this heterogeneity by defining subtypes of patients with homogeneous biological and clinical characteristics and second match these subtypes to cell lines for which extensive pharmacological data is available, thus linking targeted therapies to patients most likely to respond to treatment. (tudelft.nl)
  • This line of research ultimately combined with several others to identify aurora kinases as attractive targets for new cancer therapies. (umventures.org)
  • Moffitt participates in over 350 clinical trials. (moffitt.org)
  • To translate, in collaboration with physician-scientists, laboratory findings to hypothesis-driven clinical trials. (moffitt.org)
  • But it could also help increase participation in clinical trials, which would benefit both patients and the wider oncology community. (genomeweb.com)
  • As of right now, there are more than 1,100 anti-cancer compounds in clinical development, but only 3 percent of patients participate in clinical trials. (genomeweb.com)
  • Many clinical trials, about 38 percent, close for poor accrual because inclusion criteria are very stringent. (genomeweb.com)
  • Memorial Sloan Kettering Cancer Center's David Solit also spoke about the importance of including more patients in clinical trials, and showed examples of how a convergence of technologies is helping to advance researchers' understanding of cancer. (genomeweb.com)
  • However, tumor profiling and the measurement of cell-free DNA can be used to guide routine clinical care and enrollment into clinical trials. (genomeweb.com)
  • Dr.Kang's research focus is development of clinical trials with novel therapeutic agents for patients with head and neck cancers. (ucsf.edu)
  • Additionally, users from pharmaceutical organizations could benefit from the enablement of the standardized central pathology review of certain biomarkers within the context of clinical trials leveraging the ClinPx platform. (bio-itworld.com)
  • Drug candidates based on this approach have advanced to Phase 2 clinical trials, but, disappointingly, none have yet been validated in Phase 3. (umventures.org)
  • Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials. (ivi-rmainnovation.com)
  • Answer each question to find trials that best match your clinical situation. (clearityfoundation.org)
  • In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models. (rcsb.org)
  • Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. (idrblab.net)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • Investigators at Vanderbilt-Ingram, the University of Colorado in Aurora, Colo., and Biodesix Inc. in Steamboat Springs, Colo., with worldwide collaborators providing patient samples, set out to determine if a protein profile in the peripheral blood could predict clinical benefit - measured in terms of patient survival - to EGF receptor TKIs. (eurekalert.org)
  • This review focuses on the most recent clinical results of therapy in CML with the 2nd-generation TKIs (dasatinib, nilotinib) and on newer compounds currently under development. (rockstarsagainstliveearth.com)
  • CHD1 plays a critical role in controlling AURKA activation and promoting Aurora kinase inhibitor sensitivity, providing a potential clinical biomarker to guide cancer treatment. (figshare.com)
  • The AURKC gene provides instructions for making a protein called aurora kinase C. This protein is abundant in male testes, which are the male reproductive organs in which sperm are produced and stored. (medlineplus.gov)
  • An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
  • The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.com)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
  • In yeast, the ortholog of the Aurora B-INCENP protein kinase complex (Ipl1-Sli15) may have a role in this crucial process, because it is necessary to prevent attachment of sister kinetochores to microtubules from the same spindle pole. (pasteur.fr)
  • A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis. (medlineplus.gov)
  • The research team used a genetically engineered mouse model to define the role of aurora kinases in early progression of the disease. (bio-itworld.com)
  • In contrast, less selective compounds, including from the clinical literature, did not display differential potency in TRIM37 high versus low cancer cell lines. (oricpharma.com)
  • The phosphatydilinositol-3-kinase (PI3K)/mammalian focus on of rapamycin (mTOR) pathway is a main concentrate of attention for cancers researchers before decade. (biomasswars.com)
  • Aurora kinases are found in all organisms in which their function has been conserved throughout evolution, namely the control of chromosome segregation. (lookformedical.com)
  • Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. (pasteur.fr)
  • Preclinical results for VX-680 reported by Vertex scientists in early 2004 demonstrated for the first time that a compound targeting the Aurora mechanism could induce tumor regression in human models of solid tumor cancers. (vrtx.com)
  • Currently, multiple clinical studies investigating the therapeutic effects of the irreversible ODC inhibitor 2-difluoromethylornithine (DFMO) on neuroblastoma, astroglioma and other cancers are underway (16C18). (ubatubasat.com)
  • The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)
  • Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. (medscape.com)
  • Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. (medscape.com)
  • Identification of a new recurrent aurora kinase C mutation in both European and African men with macrozoospermia. (medlineplus.gov)
  • Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. (ucsf.edu)
  • Patients with multiple sclerosis are classified according to their clinical phenotype, with ~85% following a relapsing-remitting course (relapsing-remitting multiple sclerosis) characterized by recurrent, acute neurological deficits punctuating periods of latency or remission (Lublin and Reingold, 1996). (medscape.com)
  • This collaboration unites Vertex's drug discovery leadership targeting Aurora kinases with Merck's proprietary molecular profiling technologies and clinical development infrastructure in oncology. (vrtx.com)
  • Journal of clinical oncology, 29(6), pp. 626-31. (unibe.ch)
  • Ross Camidge, MD, PhD , of the University of Colorado Cancer Center, Aurora, is the corresponding author for the Journal of Clinical Oncology article. (ascopost.com)
  • The investigators are currently working with the Eastern Cooperative Oncology Group to develop a prospective national phase III trial that will test the prediction method's clinical benefit in lung cancer patients who are just beginning treatment for advanced disease. (eurekalert.org)
  • Path Presenter , a pioneer in the development of digital pathology software, and 4D Path Inc. , developer of a pan-cancer diagnostic and precision oncology platform enabling AI-based biomarker typing and prognostication from H&E images, announced a global partnership to distribute 4D Q-plasia OncoReader Breast within PathPresenter's new Clinical Workflow Platform, ClinPx . (bio-itworld.com)
  • Selinexor, an inhibitor of XPO1, has shown preclinical and clinical activity in sarcoma. (aacrjournals.org)
  • Therefore, it is important to explore candidate genes that could have significance to the clinical diagnosis, as well as the treatment of esophageal squamous cell carcinoma (ESCC) at the molecular level [ 4 ]. (hindawi.com)
  • In addition, the companies will conduct a joint research program to characterize VX-680's activity across a broad range of cancer types as well as to identify follow-on drug candidates directed at Aurora kinases, using molecular profiling approaches and microarray technologies pioneered by Merck. (vrtx.com)
  • Notably, further dividing these two subtypes using iNMF (iterative Non-negative Matrix Factorization) revealed five subtypes that exhibit activation of specific signaling pathways, and show significant differences in clinical and molecular characteristics. (tudelft.nl)
  • Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION. (lookformedical.com)
  • NEW YORK - Now entering its fourth stage and 16th year, the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) project is one of the longest running and best funded initiatives in the proteomics field. (genomeweb.com)
  • However, overexpression of aurora-A in particular cell lines such as NIH3T3 is sufficient to induce growth on soft agar. (lookformedical.com)
  • Concurrent chemoradiotherapy is still the mainstay of HNSCCs treatment, especially in unresectable ones, which has been associated with variable individual clinical outcomes despite similar clinical-pathological features (Nogueira et al. (researchsquare.com)
  • We compared antiviral responses to entecavir in the two groups, and evaluated the effects of entecavir on the clinical outcomes of curatively-treated Sotrastaurin solubility dmso HCC patients. (aurorakinaseb.com)
  • More data on these technologies' direct impact on objective clinical outcomes are still needed. (bvsalud.org)
  • Drug-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. (bvsalud.org)
  • An investigational new drug application (IND) for VX-680 has been filed by Vertex with the U.S. Food and Drug Administration (FDA) to support clinical development in the United States. (vrtx.com)
  • On the other side clinical studies have reported significant toxicities in a phase I trial which is usually testing the combination of an AKT inhibitor and a MEK inhibitor. (biomasswars.com)
  • Merck and Vertex expect Phase I clinical studies of VX-680 to begin by the end of 2004. (vrtx.com)
  • Left untreated the disease inexorably progresses to blastic phase (BP), defined by the presence of 30% or more blasts in the bone marrow and a clinical picture indistinguishable from acute leukemia. (rockstarsagainstliveearth.com)
  • Jones D, Noble M, Wedge SR, Robson CN, Gaughan L. Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer . (ncl.ac.uk)
  • 2012) ESMO Guidelines Working Group Nonepithelial Ovarian Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (scholarena.co)
  • In the absence of pathognomonic clinical findings or a definitive laboratory test, the diagnosis of multiple sclerosis remains challenging in many patients, and diagnostic criteria emphasize the caveat of 'no better explanation' for a patient's clinical presentation and MRI findings. (medscape.com)
  • Human umbilical cord platelet-rich plasma to treat endometrial pathologies: methodology, composition and pre-clinical models. (ivi-rmainnovation.com)
  • Merck will fund research conducted jointly by the two companies, and lead the clinical development of VX-680 and any subsequent compounds selected from the joint research program, with development input from Vertex. (vrtx.com)
  • Clinical lung cancer, 11(4), pp. 238-42. (unibe.ch)
  • Clinical lung cancer, 11(2), pp. 80-1. (unibe.ch)
  • This agreement places a significant value on our innovations in the area of Aurora kinases and cancer, and highlights Vertex's progress in realizing our 2004 business development and collaborative revenue objectives," Boger added. (vrtx.com)
  • Because of these results, a human clinical trial with selinexor in combination with a proteasome inhibitor is planned for the treatment of sarcoma. (aacrjournals.org)
  • Whitehouse Station, NJ and Cambridge, MA, June 22, 2004 -- Merck & Co., Inc. (NYSE: MRK) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that they have entered into a global collaboration to develop and commercialize VX-680, Vertex's lead Aurora kinase inhibitor that is expected to enter clinical development this year for the treatment of cancer. (vrtx.com)
  • Are you currently (or have you been) in a Clinical Trial? (breastcancer.org)
  • Despite the fact that we analyzed all EST clones covering part of the BCLL sequence, we targeted our review on these clones which have both MG-132 clinical trial selleck insertions or deletions in comparison with previously cloned BCLL mRNA variants , as a way to exclude sequences derived from genomic DNA contamination. (mirnamimic.com)
  • Clinical trial and results. (ivi-rmainnovation.com)
  • A water-mediated allosteric network governs activation of Aurora kinase A . Cyphers S, Ruff E, Behr JM, Chodera JD , and Levinson NM. (mskcc.org)