A5074914556- Cancer-related gene regulation
- ATP Synthase and ATPases Research
- Biochemical and Molecular Research
- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Research Studies
- HIV/AIDS drug development and treatment
- HIV-related health complications and treatments
- Synthesis and Catalytic Reactions
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- HIV/AIDS Research and Interventions
- Colorectal Cancer Treatments and Studies
- Cancer therapeutics and mechanisms
- Chronic Lymphocytic Leukemia Research
- Viral Infections and Vectors
- Acute Lymphoblastic Leukemia research
- Vector-Borne Animal Diseases
- HIV Research and Treatment
- Epigenetics and DNA Methylation
- Pneumocystis jirovecii pneumonia detection and treatment
- Toxoplasma gondii Research Studies
- Viral Infections and Outbreaks Research
- Protein Kinase Regulation and GTPase Signaling
- Psychedelics and Drug Studies
Mirati Therapeutics (United States)
2020-2025
Bristol-Myers Squibb (United States)
2025
Central and North West London NHS Foundation Trust
2022-2024
Mortimer Market Centre
2014-2024
RIKEN BioResource Research Center
2023
Florida College
2020-2022
University of Florida
2020-2022
Chelsea and Westminster Hospital
2005-2011
The PRMT5•MTA complex has recently emerged as a new synthetically lethal drug target for the treatment of
Abstract Previous studies implicated protein arginine methyltransferase 5 (PRMT5) as a synthetic lethal target for MTAP-deleted (MTAP del) cancers; however, the pharmacologic characterization of small-molecule inhibitors that recapitulate phenotype has not been described. MRTX1719 selectively inhibited PRMT5 in presence MTA, which is elevated MTAP del cancers, and PRMT5-dependent activity cell viability with >70-fold selectivity HCT116 compared wild-type (WT) cells. demonstrated...
Contents 1 Introduction7 1.1 Scope and purpose7 1.2 Methodology7 1.2.1 Guideline development process7 1.2.2 Involvement of people living with HIV8 1.2.3 GRADE8 1.2.4 Good practice points9 1.2.5 Dissemination implementation9 1.2.6 updates date next review9 1.3 Treatment aims9 1.4 Resource use9 1.5 Implications for research10 1.6 References10 2 Summary recommendations11 3 Active involvement HIV in decision-making11 4 When to start11 4.1 Established infection11 4.2 Same-day ART initiation11 4.3...
KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of RTK/MAPK pathway. The Son Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for RAS subfamily small GTPases represents druggable target Using structure-based drug discovery approach, MRTX0902 was identified selective potent SOS1 inhibitor that disrupts KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated on translates...
Abstract Background: KRAS inhibitors are revolutionizing the treatment of NSCLC, but clinico-genomic determinants efficacy warrant continued exploration. Methods: Patients with advanced KRASG12C-mutant NSCLC treated adagrasib (KRYSTAL-1-NCT03785249) were included in analysis. Pre-treatment NGS data collected per protocol. HTG EdgeSeq Transcriptome Panel was used for gene expression profiling. Clinical endpoints objective response, progression-free and overall survival. cell lines xenograft...
Palliative care (PC) consultation in high-risk patients with liver disease who are undergoing transplant (LT) evaluation is underused due to common beliefs that PC would negatively impact a patient’s desire for transplant. This population at risk high morbidity, mortality, and negative overall quality of life. A 4-week pilot study was conducted surgical intensive unit single academic center increase during inpatient LT improve transitions care. Two Plan, Do, Study, Act improvement cycles...
<p>Supplementary Methods S1. LKB1/<i>KEAP1</i> over-expression; Western Blot Analysis; KRAS-GTP Pull-Down Assay.</p>
<p>Supplementary Figure S2. <i>In vitro</i> efficacy of adagrasib in <i>KRAS</i><sup><i>G12C</i></sup>-mutant lung cancer models based on <i>STK11</i>/LKB1 and <i>KEAP1</i> status.</p>
<p>Supplementary Figure S6. Correlation of NRF2 score and survival to adagrasib monotherapy according <i>KEAP1</i> <i>STK11</i> co-mutation status.</p>
<p>Supplementary Figure S3. Adagrasib combination drug screens in KRASG12C-mutant lung cancer models.</p>
<p>Supplementary Figure S4. NRF2 score in KRASG12C-mutant NSCLC patients treated with adagrasib.</p>
<p>Supplementary Figure S8. <i>STK11</i>/LKB1 and epithelial-mesenchymal transition – EMT scores in <i>KRAS</i><sup><i>G12C</i></sup>-mutant NSCLC patients treated with adagrasib.</p>
<p>Supplementary Figure S1. Clinical outcomes to adagrasib monotherapy according <i>TP53</i>, <i>ATM</i> and <i>CDKN2A</i> co-mutation status.</p>
<p>Supplementary Figure S5. NRF2 score is associated with survival upon treatment adagrasib monotherapy.</p>
<p>Supplementary Figure S7. Clinical outcomes to adagrasib monotherapy according NRF2 score and <i>STK11</i> co-mutation status in <i>KEAP1</i><sup><i>WT</i></sup>/<i>KRAS</i><sup><i>G12C</i></sup>-mutant NSCLC patients.</p>
<div>AbstractPurpose:<p>KRAS inhibitors are revolutionizing the treatment of non–small cell lung cancer (NSCLC), but clinico-genomic determinants efficacy warrant continued exploration.</p>Experimental Design:<p>Patients with advanced <i>KRAS</i><sup><i>G12C</i></sup>-mutant NSCLC treated adagrasib [KRYSTAL-1 (NCT03785249)] were included in analysis. Pretreatment next-generation sequencing data collected per protocol. HTG EdgeSeq...
Abstract Protein arginine methyltransferase 5 (PRMT5) is a synthetic lethal target in cancers harboring genomic deletions of the MTAP gene, which encodes enzyme methylthioadenosine phosphorylase. Approximately one four pancreatic ductal adenocarcinoma (PDAC) cases harbor homozygous deletion gene (MTAP-del), providing promising novel targeted therapy for PDAC. The (MTA)-cooperative PRMT5 inhibitor BMS-986504 (previously known as MRTX1719) leverages elevated MTA levels present MTAP-del tumors...
The H1047R mutation of PIK3CA is highly prevalent in breast cancers and other solid tumors. Selectively targeting PI3KαH1047R over PI3KαWT crucial due to the role that plays normal cellular processes, including glucose homeostasis. Currently, only one PI3KαH1047R-selective inhibitor has progressed into clinical trials, while three pan mutant (H1047R, H1047L, H1047Y, E542K, E545K) selective PI3Kα inhibitors have also reached stage. Herein, we report design discovery a series...
Human immunodeficiency virus type 1 (HIV-1) appears to adversely affect hepatitis C, but whether C (HCV) has a reciprocal effect on HIV-1 infection remains point of controversy. In multivariate analysis cohort 5832 individuals, we found that individuals coinfected with HCV and (prevalence coinfection, 5.8%) had CD4+ cell count decreased at rate similar for infected alone. However, coinfection was associated statistically significant increased likelihood onset an acquired syndromedefining...
Non-cirrhotic portal hypertension (NCPH) has been associated with didanosine (ddl) exposure. We aimed to determine the number of individuals NCPH within our cohort and define their characteristics. identified performed a retrospective case note review. Cumulative antiretroviral therapy (ART) use was calculated statistical analysis compare exposure rest clinic for same time period. Where available, data collated on FibroScan ® , echocardiography coagulation profile. Seventeen patients were...
Abstract MRTX1719 is an MTA-cooperative PRMT5 inhibitor that leverages the increased concentration of metabolite MTA in cancer cells harboring a homozygous deletion MTAP gene (MTAP del) under investigation clincial trials. preferentially binds to PRMT5•MTA complex selectively inhibit PRMT5, essential for all cells, del while sparing activity normal MTAP-wildtype cells. occurs ~10% cancers, and these patients exhibit remarkably poor survival. Among pancreatic cancer, ~ 25% ~30% have...