A5018361694- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Colorectal Cancer Treatments and Studies
- PI3K/AKT/mTOR signaling in cancer
- Chronic Lymphocytic Leukemia Research
- HER2/EGFR in Cancer Research
- Pancreatic and Hepatic Oncology Research
- Chronic Myeloid Leukemia Treatments
- Cancer-related molecular mechanisms research
- Multiple Myeloma Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Context-Aware Activity Recognition Systems
- Analytical Chemistry and Chromatography
- Dialysis and Renal Disease Management
- Connexins and lens biology
- Erythrocyte Function and Pathophysiology
- Spectroscopy and Chemometric Analyses
- Radiomics and Machine Learning in Medical Imaging
- Acute Kidney Injury Research
- Ubiquitin and proteasome pathways
- Spectroscopy Techniques in Biomedical and Chemical Research
- Extracellular vesicles in disease
- Natural Compounds in Disease Treatment
Takeda (United States)
2017-2025
The University of Adelaide
2023-2025
Novo Nordisk (United States)
2023-2024
University of California, San Francisco
2018-2023
Dicerna Pharmaceuticals (United States)
2023
Queen Elizabeth Hospital
2023
Millennium Engineering and Integration (United States)
2017-2021
UCSF Helen Diller Family Comprehensive Cancer Center
2018-2021
University of Waterloo
2020
Regional Municipality of Waterloo
2020
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...
Post-transcriptional regulation of RNA stability is a key step in gene expression control. We describe regulatory program, mediated by the binding protein TARBP2, that controls nucleus. TARBP2 to pre-mRNAs results increased intron retention, subsequently leading targeted degradation TARBP2-bound transcripts. This recruitment m6A methylation machinery its target transcripts, where deposition marks influences splicing regulators, inhibiting efficient splicing. Interactions between and...
Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report systematic effort to decipher RNA structural code shapes pathological during breast cancer metastasis. We discovered previously unknown enhancer enriched near cassette exons with increased inclusion in highly metastatic cells. show spliceosomal protein small nuclear ribonucleoprotein polypeptide A' (SNRPA1) interacts these enhancers...
Abstract Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, address this, we used ribosome profiling compare genome-wide translation efficiencies and highly metastatic breast patient-derived xenografts. We developed dedicated regression-based methods analyse alternative...
Mobocertinib is a kinase inhibitor designed to selectively target epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer. This drug-drug interaction study assessed the effect of multiple-dose administration mobocertinib on pharmacokinetics (PK) midazolam, sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic cancer refractory/intolerant standard available therapy were enrolled. In Cycle 1 (Part A; PK cycle),...
9015 Background: TAK-788 is an investigational TKI with potent, selective preclinical activity against activating EGFR and HER2 mutations, including exon 20 insertions. We report the first results of a phase 1/2 first-in-human, open-label, multicenter study (NCT02716116). Methods: Pts advanced NSCLC refractory to standard therapy received daily oral doses (5–120 mg) in ongoing dose-escalation (3+3 design). Preliminary antitumor (by RECIST v1.1), safety, PK are reported for pts receiving ≥1...
Abstract Mobocertinib (TAK-788) is a first-in-class oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that received accelerated approval for the treatment of patients with non-small cell lung cancer EGFR exon 20 insertion mutations previously treated platinum-based chemotherapy. This phase 1, 2-period, study was conducted to assess absolute bioavailability mobocertinib (Period 1), as well mass balance, pharmacokinetics, metabolism, and excretion [ 14 C]-mobocertinib 2)...
BMS-641988 is an androgen receptor antagonist with increased potency relative to bicalutamide in both vitro and vivo prostate cancer models. A first-in-man phase I study was conducted define the safety tolerability of oral patients castration-resistant (CRPC).Doses were escalated from 5 150 mg based on discrete pharmacokinetic parameters cohorts three six subjects. After establishing 20 United States, a companion opened Japan assess differences drug metabolism between populations.Sixty-one...
Mobocertinib (TAK-788) is an investigational oral tyrosine kinase inhibitor targeting epidermal growth factor receptor and human 2. A phase 1 open-label, 2-period, fixed-sequence, 2-part study (NCT03928327) characterized effects of a strong CYP3A4 (itraconazole) inducer (rifampin) on the pharmacokinetics (PK) mobocertinib its active metabolites, AP32960 AP32914. Healthy volunteers (n = 12 per part) received single dose alone (20 mg, part 1; 160 2) with multiple doses itraconazole 200 mg once...
Abstract Nedosiran is an investigational RNA‐interference therapeutic in development for primary hyperoxaluria (PH). Because nedosiran undergoes renal clearance, we assessed its pharmacokinetic profile non‐PH participants with normal kidney function and Stages 4/5 chronic disease (CKD), the latter with/without dialysis. exposure–response modeling patients PH Subtype 1 (PH1) different level was performed to recommend a dose this subpatient population. In open‐label, single‐dose, Phase study,...
Mobocertinib is an oral tyrosine kinase inhibitor approved for treatment of patients with locally advanced or metastatic non-small cell lung cancer (mNSCLC) epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20ins) mutations previously treated platinum-based chemotherapy. These exposure-response analyses assessed potential relationships between exposure and efficacy safety outcomes in platinum-pretreated EGFRex20ins-positive mNSCLC who received mobocertinib 160 mg once daily...
The oral proteasome inhibitor ixazomib has been approved by regulatory authorities around the world, including in United States and European Union, for treatment of patients with multiple myeloma (MM) who have received at least one prior therapy, based on pivotal phase III TOURMALINE-MM1 study. objective this study was to quantitatively characterize benefit–risk profile relapsed/refractory MM support dose schedule. We report early-phase data exposure–response analyses that selection...
Abstract Mobocertinib (TAK‐788) is a tyrosine kinase inhibitor under investigation for treatment of non–small cell lung cancer with activating EGFR exon 20 insertions. This study examined the safety; tolerability; pharmacokinetics (PK), including food effects; and bioavailability mobocertinib in healthy volunteers. In part 1, fasted volunteers were randomized to placebo or single‐ascending‐dose cohorts (20‐160 mg). 2, (120/160 mg) was administered on day 1 periods 2 low‐fat meal conditions...
(3<i>R</i>,4<i>R</i>)-4-Amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-<i>f</i>][1,2,4]triazin-5-yl)methyl)-3-piperidinol (BMS-690514), an oral selective inhibitor of human epidermal growth factor receptors 1 (or receptor), 2, and 4, vascular endothelial 1, 3, is being developed as a treatment for patients with non–small-cell lung cancer metastatic breast cancer. The disposition [<sup>14</sup>C]BMS-690514 was investigated in nine healthy male subjects (group <i>n</i> = 6; group 3) after...
Resection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression serve as a prognostic marker survival after CRLM resection.MiR-203 was significantly overexpressed tumors short-term survivors compared long-term survivors. R1/R2 margin status high clinical risk score (CRS) were also...