Browsing Cancer Therapeutics by title
Now showing items 21-40 of 641
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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.
(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 Open-Label Study to Identify a Dosing Regimen of the Pan-AKT Inhibitor AZD5363 for Evaluation in Solid Tumors and in PIK3CA-Mutated Breast and Gynecologic Cancers.
(AMER ASSOC CANCER RESEARCH, 2017-10-24)Purpose: This phase I, open-label study (Study 1, D3610C00001; NCT01226316) was the first-in-human evaluation of oral AZD5363, a selective pan-AKT inhibitor, in patients with advanced solid malignancies. The objectives ... -
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.
(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 study to assess afatinib in combination with carboplatin or with carboplatin plus paclitaxel in patients with advanced solid tumors.
(SPRINGER, 2018-11-01)PURPOSE: Afatinib, an irreversible ErbB family blocker, has demonstrated preclinical antitumor activity with chemotherapy. METHODS: As part of a phase I trial in patients with advanced solid tumors (NCT00809133; 3 + 3 ... -
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.
(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 ... -
A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days.
(NATURE PUBLISHING GROUP, 2007-01-15)Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range ... -
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.
(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 ... -
A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration.
(AMER ASSOC ADVANCEMENT SCIENCE, 2020-06-23)Receptor tyrosine kinases (RTKs) are often overexpressed or mutated in cancers and drive tumor growth and metastasis. In the current model of RTK signaling, including that of MET, downstream phosphatidylinositol 3-kinase ... -
A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.
(NATURE PUBLISHING GROUP, 2020-06-26)Tumour-associated KRAS mutations are the most prevalent in the three RAS-family isoforms and involve many different amino-acids. Therefore, molecules able to interfere with mutant KRAS protein are potentially important for ... -
A risk-based approach to experimental early phase clinical trials during the COVID-19 pandemic.
(ELSEVIER SCIENCE INC, 2020-07-01) -
A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.
(NATURE PUBLISHING GROUP, 2015-12-01)There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT ... -
A streamlined workflow for single-cells genome-wide copy-number profiling by low-pass sequencing of LM-PCR whole-genome amplification products.
(PUBLIC LIBRARY SCIENCE, 2018-03-01)Chromosomal instability and associated chromosomal aberrations are hallmarks of cancer and play a critical role in disease progression and development of resistance to drugs. Single-cell genome analysis has gained interest ... -
A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials.
(ELSEVIER SCI LTD, 2018-11-01)BACKGROUND: The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I clinical trials are unknown. The objective of this study is to evaluate the incidence and severity of EAs, graded according ... -
A study of motivations and expectations of patients seen in phase 1 oncology clinics.
(WILEY-BLACKWELL, 2016-11-15)BACKGROUND: To better inform clinical practice, this study was aimed at capturing patients' motivations for enrolling in phase 1 trials and at quantifying their expectations of the benefits, risks, and commitment associated ... -
A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments.
(PUBLIC LIBRARY SCIENCE, 2017-10-05)We investigated PD-L1 changes in response to MEK and AKT inhibitors in KRAS mutant lung adenocarcinoma (adeno-NSCLC). PD-L1 expression was quantified using immunofluorescence and co-culture with a jurkat cell-line transfected ... -
A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity.
(SPRINGERNATURE, 2020-08-18)BACKGROUND: AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes of AKT inhibitors have been in clinical development, ... -
A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations.
(ELSEVIER SCI LTD, 2019-11-01)BACKGROUND: For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed. METHODS: We have developed a hybrid-capture next-generation ... -
Accelerating drug development for neuroblastoma: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma.
(ELSEVIER SCI LTD, 2020-09-01)Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 ... -
Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders.
(AMER CHEMICAL SOC, 2020-04-23)Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). ...