Browsing by author "Ruddle, Ruth"
Now showing items 1-14 of 14
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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 Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer.
Banerjee, S; Michalarea, V; Ang, JE; Ingles Garces, A; Biondo, A; et al. (AMER ASSOC CANCER RESEARCH, 2022-11-01)PURPOSE: CT900 is a novel small molecule thymidylate synthase inhibitor that binds to α-folate receptor (α-FR) and thus is selectively taken up by α-FR-overexpressing tumors. PATIENTS AND METHODS: A 3+3 dose escalation ... -
ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.
Carvalho, D; Taylor, KR; Olaciregui, NG; Molinari, V; Clarke, M; et al. (NATURE PUBLISHING GROUP, 2019-05-09)Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug ... -
Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.
Hill, RM; Kuijper, S; Lindsey, JC; Petrie, K; Schwalbe, EC; et al. (CELL PRESS, 2015-01-12)We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, ... -
Dual blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) pathways synergistically inhibits rhabdomyosarcoma cell growth in vitro and in vivo.
Renshaw, J; Taylor, KR; Bishop, R; Valenti, M; De Haven Brandon, A; et al. (AMER ASSOC CANCER RESEARCH, 2013-08-05)PURPOSE: To provide rationale for using phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathway inhibitors to treat rhabdomyosarcomas, a major cause of pediatric and adolescent cancer deaths. ... -
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 ... -
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 ... -
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 ... -
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
Yogev, O; Barker, K; Sikka, A; Almeida, GS; Hallsworth, A; et al. (AMER ASSOC CANCER RESEARCH, 2016-09-29)Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare ... -
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 ... -
Repurposing Vandetanib plus Everolimus for the Treatment of ACVR1-Mutant Diffuse Intrinsic Pontine Glioma.
Carvalho, DM; Richardson, PJ; Olaciregui, N; Stankunaite, R; Lavarino, C; et al. (AMER ASSOC CANCER RESEARCH, 2022-02-01)Somatic mutations in ACVR1 are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to ... -
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 ... -
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 ...