A5024429356- Advanced Breast Cancer Therapies
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Acute Myeloid Leukemia Research
- Cancer Treatment and Pharmacology
- Cancer-related cognitive impairment studies
- Chronic Myeloid Leukemia Treatments
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Carcinogens and Genotoxicity Assessment
- Social Policies and Family
- French Urban and Social Studies
- Cancer therapeutics and mechanisms
- Cancer Cells and Metastasis
- Aging, Elder Care, and Social Issues
- Immunotoxicology and immune responses
- Developmental Biology and Gene Regulation
- Pancreatic function and diabetes
- Biosimilars and Bioanalytical Methods
- Hedgehog Signaling Pathway Studies
- Animal testing and alternatives
Pfizer (United States)
2013-2024
La Jolla Pharmaceutical (United States)
2013
Abstract Purpose: Palbociclib (PD-0332991) is the first selective cyclin-dependent kinase (CDK) 4/6 inhibitor approved for metastatic breast cancer. Hematologic effects, especially neutropenia, are dose-limiting adverse events palbociclib in humans. Experimental Design: Reversible hematologic effects and bone marrow hypocellularity have been identified toxicology studies rats dogs after treatment. To understand mechanism by which toxicity occurs, to further differentiate it from...
The two-year cancer bioassay in rodents remains the primary testing strategy for in-life screening of compounds that might pose a potential hazard. Yet experimental evidence shows is often secondary to biological precursor effect, mode action sometimes not relevant humans, and key events leading from nongenotoxic agents usually occur well before tumorigenesis at same or lower doses than those producing tumors. International Life Sciences Institute (ILSI) Health Environmental (HESI)...
Bevacizumab, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), is approved for treatment of metastatic colorectal cancer, nonsquamous non-small-cell lung kidney and glioblastoma. To support clinical development the potential bevacizumab biosimilar PF-06439535, nonclinical studies evaluated structural, functional, toxicological, toxicokinetic similarity to sourced from European Union (bevacizumab-EU) United States (bevacizumab-US). Peptide...
Abstract Recently three different cyclin-dependent kinase 4 and 6 (CDK4/6) dual inhibitors were approved for the treatment of breast cancer (palbociclib, ribociclib, abemaciclib), all which offer comparable therapeutic benefits. Their safety profiles, however, are different. For example, neutropenia is observed at varying incidences in patients treated with these drugs; it most common adverse event palbociclib whereas diarrhea abemaciclib. To understand mechanism drugs an effort to guide...
Detecting and monitoring exocrine pancreatic damage during nonclinical clinical testing is challenging because classical biomarkers amylase lipase have limited sensitivity specificity. Novel for drug-induced injury are needed to improve safety assessment reduce late-stage attrition rates. In a series of studies, miR-216a miR-217 were evaluated as potential acute toxicity in rats. Our results revealed that almost exclusively expressed rat pancreas circulating significantly increased rats...
Abstract The degradation tag (dTAG) system for target protein can remove proteins from biological systems without the drawbacks of some genetic methods, such as slow kinetics, lack reversibility, low specificity, and inability to titrate dosage. These make it difficult compare toxicity resulting pharmacological interventions, especially in vivo. Because dTAG has not been studied extensively vivo, we explored use this study physiological sequalae CDK2 or CDK5 adult mice. Mice with homozygous...
Mortality due to acute myeloid leukemia (AML) remains high, and the management of relapsed or refractory AML continues be therapeutically challenging. The reapproval Mylotarg, an anti-CD33-calicheamicin antibody-drug conjugate (ADC), has provided a proof concept for ADC-based therapeutic AML. Several other ADCs have since entered clinical development AML, but met with limited success. We sought develop next-generation ADC wide index (TI) that overcomes shortcomings previous generations...
Abstract Genetic deletion of cyclin-dependent kinase 4 (Cdk4) is associated with pancreatic beta cell loss and glucose dysregulation in rodents. Palbociclib, one the first selective CDK4/6 inhibitors approved for treatment advanced breast cancer, currently being investigated as an adjuvant patients early-stage cancer a variety cancers covering wide-range patient populations. Hence, longer chronic toxicity studies were necessary to further examine its safety profile. The effects different...
Lorlatinib is a potent small-molecule anaplastic lymphoma kinase inhibitor approved for the treatment of patients with nonsmall cell lung cancer. In drug-drug interaction study in healthy human participants, liver enzyme elevations were observed when single 100 mg dose lorlatinib was administered after multiple doses rifampin, strong cytochrome P450 (CYP) 3A inducer and pregnane X receptor (PXR) agonist. A series vitro vivo studies conducted to evaluate potential mechanisms clinical...
The development of transforming growth factor
Abstract DNA targeting drugs represent one of cornerstones anti-cancer therapy for both hematologic and solid tumor indications. Low potency anti-DNA compounds (e.g. platins, anthracyclines) are included in many standard-of-care (SOC) regimens, however their modest activity overall toxicity profiles limit therapeutic potential. To increase the window DNA-damaging agents, high with enhanced anti-tumor have been delivered to tumors as payloads modalities such antibody-drug conjugates (ADCs)....
<div>Abstract<p><b>Purpose:</b> Palbociclib (PD-0332991) is the first selective cyclin-dependent kinase (CDK) 4/6 inhibitor approved for metastatic breast cancer. Hematologic effects, especially neutropenia, are dose-limiting adverse events palbociclib in humans.</p><p><b>Experimental Design:</b> Reversible hematologic effects and bone marrow hypocellularity have been identified toxicology studies rats dogs after treatment. To understand...
<p>Supplementary tables & figures</p>
<p>Supplementary references are listed for supplementary table S1.</p>
<p>Supplementary figure legends</p>
<p>Supplementary Table S1-2. S1 - Clinical exposure for palbociclib, fulvestrant and chemotherapeutic agents used in this study. S2 Cell cycle analysis human bone marrow mononuclear cells treated with palbociclib 4 days. Supplementary Figure S1-4. Microscopic images of sternum taken from A) a female dog vehicle control B) at 3 mg/kg/day 274 Assessment lineage-specific effects treatment CD34+ hematopoietic stem cells. S3 effect peripheral blood (hPBMCs). S4 relative estrogen receptor...
<p>Supplementary tables & figures</p>