Browsing ICR Divisions by author "Swales, Karen"
Now showing items 1-13 of 13
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A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors.
Mateo, J; Ganji, G; Lemech, C; Burris, HA; Han, S-W; et al. (AMER ASSOC CANCER RESEARCH, 2017-10-01)Background: The PI3K/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on- and off-target effects of ... -
A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.
Kolinsky, MP; Rescigno, P; Bianchini, D; Zafeiriou, Z; Mehra, N; et al. (ELSEVIER, 2020-02-21)BACKGROUND: Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence ... -
A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours.
Jamieson, D; Griffin, MJ; Sludden, J; Drew, Y; Cresti, N; et al. (ELSEVIER SCI LTD, 2016-11-01)PURPOSE: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, ... -
A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.
Vormoor, B; Veal, GJ; Griffin, MJ; Boddy, AV; Irving, J; et al. (WILEY, 2017-06-01)Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and ... -
Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation.
Dillon, MT; Guevara, J; Mohammed, K; Patin, EC; Smith, SA; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2024-01-16)BACKGROUNDPhase 1 study of ATRinhibition alone or with radiation therapy (PATRIOT) was a first-in-human phase I study of the oral ATR (ataxia telangiectasia and Rad3-related) inhibitor ceralasertib (AZD6738) in advanced ... -
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 ... -
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 ... -
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 ... -
Phase I Trial of the PARP Inhibitor Olaparib and AKT Inhibitor Capivasertib in Patients with BRCA1/2- and Non-BRCA1/2-Mutant Cancers.
Yap, TA; Kristeleit, R; Michalarea, V; Pettitt, SJ; Lim, JSJ; et al. (AMER ASSOC CANCER RESEARCH, 2020-10-01)Preclinical studies have demonstrated synergy between PARP and PI3K/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing ... -
Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance.
Guo, C; Sharp, A; Gurel, B; Crespo, M; Figueiredo, I; et al. (NATURE PORTFOLIO, 2023-11-30)Inflammation is a hallmark of cancer1. In patients with cancer, peripheral blood myeloid expansion, indicated by a high neutrophil-to-lymphocyte ratio, associates with shorter survival and treatment resistance across ... -
The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma.
Walton, MI; Eve, PD; Hayes, A; Henley, AT; Valenti, MR; et al. (IMPACT JOURNALS LLC, 2016-01-19)CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently ... -
Triplet Therapy with Palbociclib, Taselisib, and Fulvestrant in PIK3CA-Mutant Breast Cancer and Doublet Palbociclib and Taselisib in Pathway-Mutant Solid Cancers.
Pascual, J; Lim, JSJ; Macpherson, IR; Armstrong, AC; Ring, A; et al. (AMER ASSOC CANCER RESEARCH, 2021-01-01)Cyclin-dependent kinase 4/6 (CDK4/6) and PI3K inhibitors synergize in PIK3CA-mutant ER-positive HER2-negative breast cancer models. We conducted a phase Ib trial investigating the safety and efficacy of doublet CDK4/6 ... -
Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer.
Basu, B; Krebs, MG; Sundar, R; Wilson, RH; Spicer, J; et al. (OXFORD UNIV PRESS, 2018-07-17)BACKGROUND: We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients ...