A5072242084- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
The University of Texas MD Anderson Cancer Center
2022-2024
Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition active RAS potentially desirable. Here, we evaluated the antitumor activity RAS(ON) multiselective tricomplex inhibitor RMC-7977 and dissected mechanisms response tolerance in KRASG12C-mutant non-small cell lung cancer (NSCLC). Broad-spectrum reversible RASGTP with or without concurrent covalent targeting yielded superior differentiated across diverse...
<p>Supplementary Figure S1. Activity of RAS inhibitors in immune-competent pre-clinical models KRASG12C-mutated NSCLC.</p>
<p>Supplementary Figure S10. MAPK pathway modulation in immune and stromal cell subsets response to active RAS inhibition.</p>
<p>Supplementary Figure S2. Models and mechanisms of acquired resistance to RAS inhibitors</p>
<p>Supplementary Figure S3. Acute effects of active RAS inhibition in the KP2 and KL2 KrasG12C-mutant lung adenocarcinoma models</p>
<p>Supplementary Figure S6. Histological heterogeneity of lung tumors in the Kras<sup>G12C/+</sup>;Lkb1<sup>-/</sup>- GEM model.</p>
<p>Supplementary Figure S4. Acute inhibition of active RAS in KRASG12C-mutant lung adenocarcinoma.</p>
<p>Supplementary Figure S12. Evolution and regulatory networks of RASGTP inhibitor-tolerant persister cells.</p>
<p>Supplementary Figure S7. Single-cell atlas of tumor infiltrating lymphoid cells in response to RAS inhibition.</p>
<p>Supplementary Figure S5. Active RAS inhibition in Kras<sup>G12C/+</sup>;Lkb1<sup>-/</sup>- GEMMs.</p>
<p>Supplementary Figure S15. Clinical implications of mucinous lineage differentiation in human KRAS-mutant NSCLC cohorts</p>
<div>Abstract<p>Resistance to inactive state-selective RAS<sup>G12C</sup> inhibitors frequently entails accumulation of RAS<sup>GTP</sup>, rendering effective inhibition active RAS potentially desirable. Here, we evaluated the antitumor activity RAS(ON) multiselective tricomplex inhibitor RMC-7977 and dissected mechanisms response tolerance in <i>KRAS</i><sup><i>G12C</i></sup>-mutant non–small cell lung cancer (NSCLC)....
<p>Supplementary Figure S14. Mucinous tumor cells exhibit higher baseline expression of phospho-ERK1/2 and relative refractoriness to MAPK suppression following treatment with RMC-7977.</p>
<p>Supplementary Figure S13. Correlates of mucinous markers in human KRAS-mutant NSCLC</p>
<p>Supplementary Figure S9. Stromal cell remodeling in response to RAS inhibition.</p>
<p>Supplementary Figure S8. Myeloid cell transcriptional diversity in response to mutant-selective and broad spectrum RAS inhibitors.</p>
<p>Supplementary Figure S11. Characterization of tumor-cell transcriptional heterogeneity following RAS inhibition.</p>
Abstract Lung cancer is the leading cause of cancer-related mortality in United States. adenocarcinoma (LUAD) most common subtype and epidemiologically genetically heterogeneous. Pathologists have routinely observed phenotypic heterogeneity among LUAD primary tumors as reflected by distinct patterns tumor growth. However, despite prior implications on association immune-genomic environment prognosis, this information not utilized clinically. Herein, applying multiplatform analysis, we...