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Now showing items 11-20 of 71
First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors.
(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, ...
Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation.
(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 ...
Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with AKT1 E17K-Mutant, ER-Positive Metastatic Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2020-08-01)
PURPOSE: The activating mutation AKT1 E17K occurs in approximately 7% of estrogen receptor-positive (ER+) metastatic breast cancer (MBC). We report, from a multipart, first-in-human, phase I study (NCT01226316), tolerability ...
Phase I Trial of the PARP Inhibitor Olaparib and AKT Inhibitor Capivasertib in Patients with BRCA1/2- and Non-BRCA1/2-Mutant Cancers.
(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 ...
Exploiting evolutionary steering to induce collateral drug sensitivity in cancer.
(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 ...
Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials.
(AMER ASSOC CANCER RESEARCH, 2020-09-15)
PURPOSE: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. PATIENTS AND METHODS: A ...
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.
(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 ...
Inactivation of NF1 Promotes Resistance to EGFR Inhibition in KRAS/NRAS/BRAFV600 -Wild-Type Colorectal Cancer.
(AMER ASSOC CANCER RESEARCH, 2020-06-01)
Through the use of an unbiased, genome-scale CRISPR modifier screen, we identified NF1 suppression as a mechanism of resistance to EGFR inhibition in NRAS/KRAS/BRAFV600 -wild-type colorectal cancer cells. Reduced NF1 ...
The role of genomic profiling in adolescents and young adults (AYAs) with advanced cancer participating in phase I clinical trials.
(ELSEVIER SCI LTD, 2018-05-01)
INTRODUCTION: Adolescents and young adults (AYAs) diagnosed with cancer between ages 15-39 years may harbour germline variants associated with cancer predisposition. Such variants represent putative therapeutic targets, ...
A Phase 1, open-label, multicentre study to compare the capsule and tablet formulations of AZD5363 and explore the effect of food on the pharmacokinetic exposure, safety and tolerability of AZD5363 in patients with advanced solid malignancies: OAK.
(SPRINGER, 2018-05-01)
PURPOSE: AZD5363 is a potent pan-AKT inhibitor originally formulated as a capsule; a tablet was developed for patient convenience and manufacturing ease. This study assessed the PK comparability of both formulations (Part A) ...