A5101321974- Colorectal Cancer Treatments and Studies
- Chronic Myeloid Leukemia Treatments
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
The University of Texas MD Anderson Cancer Center
2024-2025
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...
<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 Background: KRAS G12C inhibitors (G12Ci) are revolutionizing the therapeutic landscape of advanced NSCLC, but mechanisms limited clinical efficacy observed in some patients (pts) merit continued exploration. In largest cohort G12C-mutant (KG12C) NSCLC pts treated with G12Ci, we demonstrated KEAP1 and STK11 co-mutations enriched early progression to G12Ci. Yet independent predictive role impact enhanced NRF2 signaling outcomes G12Ci remains incompletely characterized. Methods:...