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A First-in-Human, Phase I, Dose-Escalation Study of TAK-117, a Selective PI3Kα Isoform Inhibitor, in Patients with Advanced Solid Malignancies.
(2017-09)
Purpose: To evaluate the safety, MTD, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of TAK-117 (MLN1117/INK1117), an investigational PI3Kα-selective inhibitor, in patients with advanced solid tumors. ...
Dual blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) pathways synergistically inhibits rhabdomyosarcoma cell growth in vitro and in vivo.
(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. ...
Noninvasive MRI Native T1 Mapping Detects Response to MYCN-targeted Therapies in the Th-MYCN Model of Neuroblastoma.
(AMER ASSOC CANCER RESEARCH, 2020-08-15)
Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies ...
Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.
(AMER ASSOC CANCER RESEARCH, 2021-10-01)
PURPOSE: This study reports the safety, tolerability, MTD, recommended phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of ceralasertib combined with carboplatin in patients ...
Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer.
(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 ...
A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors.
(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 ...
First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014.
(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 ...
A phase 1/2 study of the combination of acalabrutinib and vistusertib in patients with relapsed/refractory B-cell malignancies.
(TAYLOR & FRANCIS LTD, 2021-07-15)
In a phase 1b study of acalabrutinib (a covalent Bruton tyrosine kinase (BTK) inhibitor) in combination with vistusertib (a dual mTORC1/2 inhibitor) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), ...