A5068078026- interferon and immune responses
- Cell death mechanisms and regulation
- Hippo pathway signaling and YAP/TAZ
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
Wellcome Sanger Institute
2020-2024
Most lung cancer patients with metastatic eventually relapse drug-resistant disease following treatment and EGFR mutant is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cell lines, revealed the landscape of pathways that cause resistance inhibitors osimertinib gefitinib cancer. Among most recurrent were those regulate Hippo pathway. Following a subpopulation cells are able survive over time develop stable resistance. These...
New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as targets. known and novel fitness genes demonstrate many previously identified OSCC-related cancer non-essential could have limited value, while other warrant further investigation their potential validate a distinctive dependency on YAP1 WWTR1 of the Hippo...
Abstract Multivalent second-generation TRAIL-R2 agonists are currently in late preclinical development and early clinical trials. Herein, we use a representative agent, MEDI3039, to address two major challenges facing these agents: lack of predictive biomarkers enable patient selection emergence resistance. Genome-wide CRISPR knockout screens were notable for the resistance mechanisms beyond canonical pathway (caspase-8, FADD, BID) as well p53 BAX TP53 wild-type models, whereas activatory...
Supplementary Data from Functional Genomic Identification of Predictors Sensitivity and Mechanisms Resistance to Multivalent Second-Generation TRAIL-R2 Agonists
Supplementary Figure from Functional Genomic Identification of Predictors Sensitivity and Mechanisms Resistance to Multivalent Second-Generation TRAIL-R2 Agonists
<div>Abstract<p>Multivalent second-generation TRAIL-R2 agonists are currently in late preclinical development and early clinical trials. Herein, we use a representative agent, MEDI3039, to address two major challenges facing these agents: lack of predictive biomarkers enable patient selection emergence resistance. Genome-wide CRISPR knockout screens were notable for the resistance mechanisms beyond canonical pathway (caspase-8, FADD, BID) as well p53 BAX TP53 wild-type models,...
Supplementary Figure from Functional Genomic Identification of Predictors Sensitivity and Mechanisms Resistance to Multivalent Second-Generation TRAIL-R2 Agonists
Supplementary Data from Functional Genomic Identification of Predictors Sensitivity and Mechanisms Resistance to Multivalent Second-Generation TRAIL-R2 Agonists
<div>Abstract<p>Multivalent second-generation TRAIL-R2 agonists are currently in late preclinical development and early clinical trials. Herein, we use a representative agent, MEDI3039, to address two major challenges facing these agents: lack of predictive biomarkers enable patient selection emergence resistance. Genome-wide CRISPR knockout screens were notable for the resistance mechanisms beyond canonical pathway (caspase-8, FADD, BID) as well p53 BAX TP53 wild-type models,...