A5091216677- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- PI3K/AKT/mTOR signaling in cancer
- Advanced Breast Cancer Therapies
- Cancer Mechanisms and Therapy
- Cancer Genomics and Diagnostics
- Peptidase Inhibition and Analysis
- Colorectal Cancer Treatments and Studies
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Cancer Treatment and Pharmacology
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- Estrogen and related hormone effects
- Molecular Biology Techniques and Applications
- Chronic Lymphocytic Leukemia Research
- Canadian Identity and History
- Multiculturalism, Politics, Migration, Gender
- Glycosylation and Glycoproteins Research
- Melanoma and MAPK Pathways
- Cellular Mechanics and Interactions
- Social Sciences and Governance
- French Urban and Social Studies
- Bioinformatics and Genomic Networks
Takeda (United States)
2018-2024
Millennium Engineering and Integration (United States)
2018-2023
Sanofi (United States)
2017-2018
Université de Montréal
2018
Sanofi (France)
2017
AVEO Oncology (United States)
2009-2014
Harvard University
1997-2007
Tufts Medical Center
2007
Brigham and Women's Hospital
2007
The University of Texas MD Anderson Cancer Center
2003
Protein interaction maps have provided insight into the relationships among predicted proteins of model organisms for which a genome sequence is available. These been useful in generating potential networks, confirmed existence known complexes and pathways suggested new or crosstalk between previously unlinked pathways. However, generation such costly labor intensive. Here, we investigate extent to protein map generated one species can be used predict interactions another species.
<h3>Importance</h3> Metastatic non–small cell lung cancer (mNSCLC) with<i>EGFR</i>exon 20 insertion (<i>EGFR</i>ex20ins) mutations is associated with a poor prognosis. Mobocertinib an oral tyrosine kinase inhibitor designed to selectively target<i>EGFR</i>ex20ins mutations. <h3>Objective</h3> To evaluate treatment outcomes and safety of mobocertinib in patients previously treated<i>EGFR</i>ex20ins-positive mNSCLC. <h3>Design, Setting, Participants</h3> This 3-part, open-label, phase 1/2...
Mobocertinib, an oral epidermal growth factor receptor (EGFR) inhibitor targeting EGFR gene mutations, including exon 20 insertions (EGFRex20ins), in non-small cell lung cancer, was evaluated a phase I/II dose-escalation/expansion trial (ClinicalTrials.gov NCT02716116). Dose escalation identified 160 mg/d as the recommended 2 dose and maximum tolerated dose. Among 136 patients treated with mg/d, most common any-grade treatment-related adverse events (TRAE; >25%) were diarrhea (83%), nausea...
Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non-small cell lung cancer (NSCLC) are insensitive to approved tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible TKI, was specifically designed potently inhibit oncogenic variants containing activating EGFRex20ins with selectivity over wild-type EGFR. The vitro and vivo activity evaluated engineered patient-derived models...
Primary papillary tumors of the central nervous system are rare. We have encountered a series six pineal region with distinctive features that appear to represent clinicopathologic entity. The occurred in four women and two men, ranging age from 19 53 years. Imaging studies showed large well-circumscribed mass region. were characterized by an epithelial-like growth pattern, which vessels covered layer tumoral cells. In areas, neoplastic cells large, columnar or cuboidal, clear cytoplasm....
The Rac and Cdc42 GTPases share several regulators effectors, yet perform distinct biological functions. factors determining such specificity in vivo have not been identified. In a mutational screen Drosophila to identify Rac-specific signaling components, we isolated 11 alleles of myoblast city ( mbc ). mutant embryos exhibit defects dorsal closure, myogenesis, neural development. DOCK180, the mammalian homolog Mbc, associates with Rac, but Cdc42, nucleotide-independent manner. These...
Journal Article S26 ribosomal protein RNA: an invariant control for gene regulation experiments in eucaryotic cells and tissues Get access Sylvie Vincent, Vincent Institut de Génétique Moléculaire MontpellierCNRS, 1919 Route Mende, BP 5051, F-34033 Montpellier cedex 2, France Search other works by this author on: Oxford Academic PubMed Google Scholar Louise Marty, Marty Philippe Fort Nucleic Acids Research, Volume 21, Issue 6, 25 March 1993, Page 1498, https://doi.org/10.1093/nar/21.6.1498...
The Ras-related Rho family GTPases mediate signal transduction pathways that regulate a variety of cellular processes.Like Ras, the proteins (which include Rho, Rac, and CDC42) interact directly with protein kinases, which are likely to serve as downstream effector targets activated GTPase.Activated RhoA has recently been reported several p120 PKN, p150 ROK␣ -, p160 ROCK, p164 kinase.Here, we describe purification novel Rho-associated kinase, p140, appears be major kinase activity in most...
EGFR exon 20 insertion (ex20ins) mutations represent 5% to 10% of in NSCLC. Identifying patients with ex20ins is challenging owing the limited coverage polymerase chain reaction (PCR) assays and relatively recent use next-generation sequencing (NGS). This study analyzes spectrum variants a large patient population from global clinical trial several real-world cohorts ability PCR kits identify these alterations.We conducted this retrospective analysis NSCLC who underwent NGS or other testing...
This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib.Patients with advanced that progressed crizotinib were randomized 1:1 to 180 mg once daily (7-d lead-in, 90 mg) or 600 twice daily, aiming test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Interim analysis futility planned at approximately 70% 164...
9007 Background: TAK-788 is an oral investigational EGFR/HER2 inhibitor under evaluation in NSCLC patients (pts) with EGFR exon 20 insertions. We report results of a phase 1/2 open-label, multicenter study (NCT02716116). Methods: Pts advanced, previously treated received daily dose escalation and expansion cohorts based on tumor genotype. Antitumor activity was determined for pts insertions who at the RP2D. Safety reported all across doses 160 mg. Results: As 14 Sep 2018, 101 (median age, 61...
Abstract No targeted treatments are currently approved for HER2 exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (HER2/ERBB2) insertion mutations. However, the function of mobocertinib on cancer still unclear. Here we conducted systematic characterization preclinical models understand activity profile against insertions. In cell lines, IC50 was...
Cellular transition from the resting state to DNA synthesis involves master switches genes encoding transcriptional factors (e.g., fos, jun, and egr genes), whose targets remain be fully characterized. To isolate coding sequences specifically accumulated in late G1, a differential screening was performed on cDNA library prepared hamster lung fibroblasts stimulated for 5 h with serum. One of positive clones which displayed sevenfold induction, turned out code protein sharing homology Ras-like...
ERBB3 is overexpressed in a broad spectrum of human cancers, and its aberrant activation associated with tumor pathogenesis therapeutic resistance to various anticancer agents. Neuregulin 1 (NRG1) the predominant ligand for can promote heterodimerization other ERBB family members, resulting multiple intracellular signaling pathways. AV-203 humanized IgG1/κ inhibitory antibody that completed first-in-human phase I clinical trial patients advanced solid tumors. The purpose this preclinical...
Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results uncontrolled growth permissive microenvironment. Accordingly, physiologically relevant models of human breast recapitulate these events are needed to study biology and evaluate therapeutic agents. Here, we report the generation utilization mouse (HIM) model, which composed genetically engineered primary organoids activated stromal cells. By using...
9014 Background: No approved targeted therapies are available for EGFR ex20ins+ mNSCLC. Mobocertinib, a first-in-class, potent, oral TKI targeting ex20ins mutations, has Breakthrough Therapy Designation in the US and China post-platinum-based chemotherapy pts with Methods: This 3-part, open-label, multicenter study (NCT02716116) dose-escalation/expansion extension (EXCLAIM) cohorts. Pts mNSCLC, ECOG status 0–1, ≥1 prior line of therapy locally advanced/metastatic disease received...
Abstract Purpose: This phase II study investigated daily or weekly sapanisertib (a selective dual inhibitor of mTOR complexes 1 and 2) in combination with fulvestrant. Patients Methods: Postmenopausal women estrogen receptor–positive (ER+)/HER2-negative (HER2−) advanced metastatic breast cancer following progression during/after aromatase treatment were randomized to receive fulvestrant 500 mg (28-day cycles), plus 4 daily, 30 weekly, until progressive disease, unacceptable toxicity, consent...
In Triton-skinned phasic ileal smooth muscle, constitutively active recombinant p21-activated kinase (PAK3) has been shown to induce Ca 2+ -independent contraction, which is accompanied by phosphorylation of caldesmon and desmin (Van Eyk JE, Arrell DK, Foster DB, Strauss JD, Heinonen TY, Furmaniak-Kazmierczak E, Cote GP, Mak AS. J Biol Chem 273: 23433–23439, 1998). the present study, we investigated whether PAK a broad impact on muscle in general testing hypothesis that induces contractions...
This open-label, multicenter, phase IB/II study evaluated sapanisertib, a dual inhibitor of mTOR kinase complexes 1/2, plus exemestane or fulvestrant in postmenopausal women with hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced/metastatic breast cancer.Eligible patients had previously progressed on everolimus exemestane/fulvestrant and received ≤3 (phase IB) ≤1 II) prior chemotherapy regimens. Patients sapanisertib 3 to 5 mg every day IB), 4 25 500 monthly 28-day cycles. Phase...
This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel TAK-117 (a selective small molecule PI3K), versus alone advanced, recurrent, persistent endometrial cancer.