A5008588037- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- DNA Repair Mechanisms
- Melanoma and MAPK Pathways
- Cutaneous Melanoma Detection and Management
University of California, Los Angeles
2023
Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), homologous recombination repair (HRR) genes via complex rearrangements (CGR) extrachromosomal DNAs (ecDNA). Almost all sensitive acquired-resistant harbor...
<p>Supplementary Figure S1. Associations of CGRs and ecDNAs with ploidy, expression, enhancers. Supplementary S2. Analysis chromothripsis, ecDNAs, in MAPKi-sensitive/-naïve versus -resistant melanoma. S3. Inferring double-stranded DNA break repair pathways underlying ecDNA CGR breakpoint junctions. S4. Single-agent inhibitory potencies human melanoma, PDAC, NSCLC clonogenic growth assays. S5. DNA-PKi and/or PARPi co-treatment prevents acquired MAPKi-resistance melanoma cell lines. S6....
<p>Supplementary Figure S1. Associations of CGRs and ecDNAs with ploidy, expression, enhancers. Supplementary S2. Analysis chromothripsis, ecDNAs, in MAPKi-sensitive/-naïve versus -resistant melanoma. S3. Inferring double-stranded DNA break repair pathways underlying ecDNA CGR breakpoint junctions. S4. Single-agent inhibitory potencies human melanoma, PDAC, NSCLC clonogenic growth assays. S5. DNA-PKi and/or PARPi co-treatment prevents acquired MAPKi-resistance melanoma cell lines. S6....
<div>Abstract<p>Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), homologous recombination repair (HRR) genes via complex rearrangements (CGR) extrachromosomal DNAs (ecDNA). Almost all...
<div>Abstract<p>Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), homologous recombination repair (HRR) genes via complex rearrangements (CGR) extrachromosomal DNAs (ecDNA). Almost all...
<p>Supplementary Figure S1. Associations of CGRs and ecDNAs with ploidy, expression, enhancers. Supplementary S2. Analysis chromothripsis, ecDNAs, in MAPKi-sensitive/-naïve versus -resistant melanoma. S3. Inferring double-stranded DNA break repair pathways underlying ecDNA CGR breakpoint junctions. S4. Single-agent inhibitory potencies human melanoma, PDAC, NSCLC clonogenic growth assays. S5. DNA-PKi and/or PARPi co-treatment prevents acquired MAPKi-resistance melanoma cell lines. S6....
<div>Abstract<p>Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), homologous recombination repair (HRR) genes via complex rearrangements (CGR) extrachromosomal DNAs (ecDNA). Almost all...
<p>Supplementary Figure S1. Associations of CGRs and ecDNAs with ploidy, expression, enhancers. Supplementary S2. Analysis chromothripsis, ecDNAs, in MAPKi-sensitive/-naïve versus -resistant melanoma. S3. Inferring double-stranded DNA break repair pathways underlying ecDNA CGR breakpoint junctions. S4. Single-agent inhibitory potencies human melanoma, PDAC, NSCLC clonogenic growth assays. S5. DNA-PKi and/or PARPi co-treatment prevents acquired MAPKi-resistance melanoma cell lines. S6....
<p>Supplementary Figure S1. Associations of CGRs and ecDNAs with ploidy, expression, enhancers. Supplementary S2. Analysis chromothripsis, ecDNAs, in MAPKi-sensitive/-naïve versus -resistant melanoma. S3. Inferring double-stranded DNA break repair pathways underlying ecDNA CGR breakpoint junctions. S4. Single-agent inhibitory potencies human melanoma, PDAC, NSCLC clonogenic growth assays. S5. DNA-PKi and/or PARPi co-treatment prevents acquired MAPKi-resistance melanoma cell lines. S6....
<div>Abstract<p>Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), homologous recombination repair (HRR) genes via complex rearrangements (CGR) extrachromosomal DNAs (ecDNA). Almost all...
<p>Supplementary Figure S1. Associations of CGRs and ecDNAs with ploidy, expression, enhancers. Supplementary S2. Analysis chromothripsis, ecDNAs, in MAPKi-sensitive/-naïve versus -resistant melanoma. S3. Inferring double-stranded DNA break repair pathways underlying ecDNA CGR breakpoint junctions. S4. Single-agent inhibitory potencies human melanoma, PDAC, NSCLC clonogenic growth assays. S5. DNA-PKi and/or PARPi co-treatment prevents acquired MAPKi-resistance melanoma cell lines. S6....