A5082517668- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Lung Cancer Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Gastric Cancer Management and Outcomes
- PI3K/AKT/mTOR signaling in cancer
- Brain Metastases and Treatment
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- Radiation Therapy and Dosimetry
- Lymphoma Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Neuroendocrine Tumor Research Advances
- Gastrointestinal Tumor Research and Treatment
- Chronic Myeloid Leukemia Treatments
- Fibroblast Growth Factor Research
- Cancer Treatment and Pharmacology
- Monoclonal and Polyclonal Antibodies Research
University of Colorado Denver
2016-2025
University of Colorado Cancer Center
2016-2025
University of Colorado Boulder
2007-2025
University of Colorado Anschutz Medical Campus
2015-2024
Pfizer (United States)
2007-2024
Medtronic (Ireland)
2024
Janssen (Italy)
2024
AstraZeneca (Brazil)
2024
Seagen (Canada)
2024
Verastem (United States)
2024
Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup non-small-cell lung cancers, representing 2 to 7% such tumors. We explored the therapeutic efficacy inhibiting ALK tumors an early-phase clinical trial crizotinib (PF-02341066), orally available small-molecule inhibitor tyrosine kinase.After screening tumor samples from approximately 1500 patients with cancer for presence rearrangements, we identified 82 advanced ALK-positive disease who...
In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine inhibitor targeting ALK. Whether crizotinib is superior standard chemotherapy respect efficacy unknown.
Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib patients previously untreated, advanced NSCLC, including those asymptomatic CNS disease.In randomized, open-label, phase 3 trial, we randomly assigned 303 NSCLC to receive either (600 mg twice daily) or (250 daily). The primary end point...
Chromosomal rearrangements of the gene encoding ROS1 proto-oncogene receptor tyrosine kinase (ROS1) define a distinct molecular subgroup non-small-cell lung cancers (NSCLCs) that may be susceptible to therapeutic inhibition. Crizotinib is small-molecule inhibitor anaplastic lymphoma (ALK), ROS1, and another kinase, MET.
Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed perform multiplexed assays testing adenocarcinomas for in 10 genes enable clinicians select targeted treatments enroll into clinical trials.To determine frequency use data targeting identified driver(s) measure survival.From 2009 through 2012, 14 sites United States enrolled metastatic a...
Non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to ALK inhibitor crizotinib, but resistance invariably develops. Ceritinib (LDK378) a new that has shown greater antitumor potency than crizotinib in preclinical studies.In this phase 1 study, we administered oral ceritinib doses of 50 750 mg once daily patients with advanced cancers genetic alterations ALK. In an expansion received maximum tolerated dose. Patients were assessed...
Our previously published findings reported that local consolidative therapy (LCT) with radiotherapy or surgery improved progression-free survival (PFS) and delayed new disease in patients oligometastatic non-small-cell lung cancer (NSCLC) did not progress after front-line systemic therapy. Herein, we present the longer-term overall (OS) results accompanied by additional secondary end points.
Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor. Unfortunately, not every patient responds and acquired drug resistance inevitably develops in those who do respond. This study aimed define molecular mechanisms of crizotinib patients ALK(+) non-small cell lung cancer (NSCLC).We analyzed tissue obtained from 14 NSCLC showing evidence radiologic progression while on intrinsic crizotinib.Eleven had...
Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The of brigatinib, as compared crizotinib, advanced NSCLC who have not previously received an ALK inhibitor unclear.In open-label, phase 3 trial, we randomly assigned, 1:1 ratio, had inhibitors receive brigatinib at dose 180 mg once daily (with 7-day lead-in period 90 mg) or crizotinib 250 twice daily....
Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by T790M most cases. Rociletinib (CO-1686) an inhibitor active preclinical models of EGFR-mutated NSCLC or without T790M.In this phase 1-2 study, we administered rociletinib patients who had disease progression during previous treatment existing inhibitor. In expansion (phase 2) part T790M-positive received...
Circulating tumour DNA (ctDNA) analysis facilitates studies of heterogeneity. Here we employ CAPP-Seq ctDNA to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple 46% after treatment first-line inhibitors, indicating frequent intra-patient Rociletinib recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. describe a novel EGFR L798I mutation...
Crizotinib is an oral kinase inhibitor approved for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). The clinical benefits crizotinib in patients with brain metastases have not been previously studied.Patients advanced NSCLC enrolled onto trial PROFILE 1005 or 1007 (randomly assigned to crizotinib) were included this retrospective analysis. Patients asymptomatic (nontarget target lesions) allowed enroll. Tumor assessments evaluated every 6 weeks using RECIST (version...
Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)–rearranged non–small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods were stratified by brain metastases best response to crizotinib. They randomly assigned (1:1) oral brigatinib 90 mg once daily (arm A) or 180 a 7-day...
Resistance to chemotherapy-induced apoptosis represents a major obstacle cancer control. Overexpression of Bcl-2 is seen in multiple tumor types and targeting may provide therapeutic benefit. A phase I study navitoclax, novel inhibitor family proteins, was conducted evaluate safety, pharmacokinetics, preliminary efficacy patients with solid tumors.Patients enrolled intermittent dosing cohorts received navitoclax on day -3, followed by days 1 14 21-day cycle. Patients continuous 1-week...
Purpose To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics, and preliminary anticancer activity of ramucirumab (IMC-1121B), a fully human immunoglobulin G 1 monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR)-2. Patients Methods with advanced solid malignancies were treated once weekly escalating doses ramucirumab. Blood was sampled for PK studies throughout treatment. The effects on circulating factor-A (VEGF-A),...
The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall (OS) up to 5 years 29 2019).Patients stage III/IV NSCLC were randomized receive twice-daily 600 mg (n = 152) or 250 151) until disease progression, toxicity, withdrawal death. Primary end point:...