Browsing Cancer Therapeutics by author "Banerji, Udai"
Now showing items 21-40 of 54
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Development and validation of a LC-MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma.
Zangarini, M; Berry, P; Sludden, J; Raynaud, FI; Banerji, U; et al. (FUTURE SCI LTD, 2017-07-01)AIM: SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1 being investigated in an oncology setting. A HPLC-MS/MS method for quantifying plasma concentrations of SRA737 was validated. METHODS & RESULTS: ... -
Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.
Stewart, A; Coker, EA; Pölsterl, S; Georgiou, A; Minchom, AR; et al. (AMER ASSOC CANCER RESEARCH, 2019-08-01)It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic ... -
Evaluation of the combination of the dual m-TORC1/2 inhibitor vistusertib (AZD2014) and paclitaxel in ovarian cancer models.
Wong Te Fong, A-C; Thavasu, P; Gagrica, S; Swales, KE; Leach, MO; et al. (IMPACT JOURNALS LLC, 2017-12-26)Activation of the PI3K/mTOR pathway has been shown to be correlated with resistance to chemotherapy in ovarian cancer. We aimed to investigate the effects of combining inhibition of mTORC1 and 2 using the mTOR kinase ... -
Exploiting evolutionary steering to induce collateral drug sensitivity in cancer.
Acar, A; Nichol, D; Fernandez-Mateos, J; Cresswell, GD; Barozzi, I; et al. (NATURE PORTFOLIO, 2020-04-21)Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another ... -
First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014.
Basu, B; Dean, E; Puglisi, M; Greystoke, A; Ong, M; et al. (AMER ASSOC CANCER RESEARCH, 2015-08-01)PURPOSE: AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and in vivo efficacy across a range of preclinical human cancer models. EXPERIMENTAL DESIGN: A rolling six-dose escalation was performed to ... -
First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors.
Shimomura, A; Yamamoto, N; Kondo, S; Fujiwara, Y; Suzuki, S; et al. (AMER ASSOC CANCER RESEARCH, 2019-03-01)HSP90 is involved in stability and function of cancer-related proteins. This study was conducted to define the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy of TAS-116, a novel class, ... -
First-in-Human Study of AT13148, a Dual ROCK-AKT Inhibitor in Patients with Solid Tumors.
McLeod, R; Kumar, R; Papadatos-Pastos, D; Mateo, J; Brown, JS; et al. (AMER ASSOC CANCER RESEARCH, 2020-09-15)PURPOSE: AT13148 is an oral AGC kinase inhibitor, which potently inhibits ROCK and AKT kinases. In preclinical models, AT13148 has been shown to have antimetastatic and antiproliferative activity. PATIENTS AND METHODS: The ... -
Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials.
Rafii, S; Roda, D; Geuna, E; Jimenez, B; Rihawi, K; et al. (AMER ASSOC CANCER RESEARCH, 2015-04-15)PURPOSE: Novel antitumor therapies against the PI3K-AKT-mTOR pathway are increasingly used to treat cancer, either as single agents or in combination with chemotherapy or other targeted therapies. Although these agents are ... -
Hyperglycemia and Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) Inhibitors in Phase I Trials: Incidence, Predictive Factors, and Management.
Khan, KH; Wong, M; Rihawi, K; Bodla, S; Morganstein, D; et al. (ALPHAMED PRESS, 2016-07-01)BACKGROUND: Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is implicated in human cancer growth and progression. Agents targeting this pathway are ... -
Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma.
Tucker, ER; Tall, JR; Danielson, LS; Gowan, S; Jamin, Y; et al. (WILEY, 2017-08-01)Targeted inhibition of anaplastic lymphoma kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies; however, the presence of resistant mutations necessitates both the development of more ... -
Individualized Prediction of Drug Response and Rational Combination Therapy in NSCLC Using Artificial Intelligence-Enabled Studies of Acute Phosphoproteomic Changes.
Coker, EA; Stewart, A; Ozer, B; Minchom, A; Pickard, L; et al. (AMER ASSOC CANCER RESEARCH, 2022-06-01)We hypothesize that the study of acute protein perturbation in signal transduction by targeted anticancer drugs can predict drug sensitivity of these agents used as single agents and rational combination therapy. We assayed ... -
Insights into significance of combined inhibition of MEK and m-TOR signalling output in KRAS mutant non-small-cell lung cancer.
Broutin, S; Stewart, A; Thavasu, P; Paci, A; Bidart, J-M; et al. (NATURE PUBLISHING GROUP, 2016-08-23)BACKGROUND: We aimed to understand the dependence of MEK and m-TOR inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cell lines. METHODS: In a panel of KRAS(M) and KRAS(WT) NSCLC cell lines, we determined growth inhibition ... -
Intermittent schedules of the oral RAF-MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study.
Guo, C; Chénard-Poirier, M; Roda, D; de Miguel, M; Harris, SJ; et al. (ELSEVIER SCIENCE INC, 2020-11-01)BACKGROUND: CH5126766 (also known as VS-6766, and previously named RO5126766), a novel MEK-pan-RAF inhibitor, has shown antitumour activity across various solid tumours; however, its initial development was limited by ... -
Maximising the potential of AKT inhibitors as anti-cancer treatments.
Brown, JS; Banerji, U (PERGAMON-ELSEVIER SCIENCE LTD, 2017-04-01)PI3K/AKT signalling is commonly disrupted in human cancers, with AKT being a central component of the pathway, influencing multiple processes that are directly involved in tumourigenesis. Targeting AKT is therefore a highly ... -
Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation.
Pal, A; Asad, Y; Ruddle, R; Henley, AT; Swales, K; et al. (SPRINGER, 2020-04-13)INTRODUCTION: To generate biomarkers of target engagement or predictive response for multi-target drugs is challenging. One such compound is the multi-AGC kinase inhibitor AT13148. Metabolic signatures of selective signal ... -
Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma.
Ang, JE; Pal, A; Asad, YJ; Henley, AT; Valenti, M; et al. (AMER ASSOC CANCER RESEARCH, 2017-10-01)MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based ... -
Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.
Minchom, A; Yuan, W; Crespo, M; Gurel, B; Figueiredo, I; et al. (BMJ PUBLISHING GROUP, 2020-03-01)BACKGROUND: This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. CASE PRESENTATION: A 77-year-old woman with advanced epithelioid ... -
Multidisciplinary interventions in a specialist Drug Development Unit to improve family history documentation and onward referral of patients with advanced cancer to cancer genetics services.
Moss, CA; Cojocaru, E; Hanwell, J; Ward, S; Xu, W; et al. (ELSEVIER SCI LTD, 2019-06-01)BACKGROUND: Molecular aberrations in cancer may represent therapeutic targets, and, if arising from the germline, may impact further cancer risk management in patients and their blood relatives. Annually, 600-700 patients ... -
Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors.
Ameratunga, M; Chénard-Poirier, M; Moreno Candilejo, I; Pedregal, M; Lui, A; et al. (ELSEVIER SCI LTD, 2018-01-01)BACKGROUND: Although the neutrophil-lymphocyte ratio (NLR) is prognostic in many oncological settings, its significance in the immunotherapy era is unknown. Mechanistically, PD-1/PD-L1 inhibitors may alter NLR. We sought ... -
PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours.
Dillon, MT; Boylan, Z; Smith, D; Guevara, J; Mohammed, K; et al. (ELSEVIER IRELAND LTD, 2018-08-01)PATRIOT is a phase I study of the ATR inhibitor, AZD6738, as monotherapy, and in combination with palliative radiotherapy. Here, we describe the protocol for this study, which opened in 2014 and is currently recruiting and ...