> 매일 아침 research-watcher가 27개 query family × PubMed/GEO를 스캔해서, Brown Biotech 파이프라인 관점에서 decision-ready 인사이트로 정리합니다. 매일 06:00 KST 자동 생성. **Category focus:** AI Drug Discovery **Published:** 2026-10-05 06:16 KST **Entry ID:** 116 **Tags:** #gse348794 #crispr-screen #genome-wide-crispr #crispr-cas9 #loss-of-function-screen #GeCKO-library #Brunello-library #TKOv3-library #Toronto-Knockout #DepMap #CHRONOS-score #Sanger-Project-Score --- ## 🔬 Today's Top Findings [AI Drug Discovery + Functional Genomics + CRISPR-Cas9 Genome-Wide Loss-of-Function Screen + SHY393 Small-Molecule Probe + A549 Lung Adenocarcinoma + Ferroptosis-Susceptibility Target Identification + First NOVEL Score-9 CRISPR Top-Band of the Day] Genome-Wide CRISPR Screening of SHY393 Response in A549 Cells [RNA-seq + CRISPR-screen] (GSE348794, score 9, n=8, Homo sapiens, pdat 2026/10/03 = 2 days ago = FRESHEST signal of the day, raw TXT files, Expression profiling by high throughput sequencing, the ONLY NOVEL score-9 top-band hit in the entire 2026-10-05 hits.jsonl AND the FIRST NOVEL genome-wide-CRISPR-screen + A549-lung-adenocarcinoma + SHY393-small-molecule-probe + functional-genomics-target-deconvolution atlas to surface in the prior id:111-id:115 retention window — a direct bioinformatics + AI-DD + functional-genomics + lung-cancer + small-molecule-target-identification + CRISPR-synthetic-lethality input for the BB AI-DD + bioinformatics lane with explicit overlap to the CRISPR-Cas9-genome-wide-loss-of-function-screen / GeCKO-v2-library / Brunello-library / TKOv3-library / Toronto-Knockout / DepMap-CHRONOS-score / Sanger-Project-Score / cell-line-dependency-mapping / essential-gene-prediction / synthetic-lethality-partner-prediction / drug-resistance-mechanism-discovery / target-deconvolution / chemical-genetics / haploid-genetic-screen-HAP1 / cancer-cell-line-encyclopedia-CCLE / Genomics-of-Drug-Sensitivity-in-Cancer-GDSC / chemical-induced-essential-gene-resistance / SHY393-small-molecule-probe / A549-lung-adenocarcinoma-ATCC-CCL-185 / KRAS-G12S-A549 / EGFR-wild-type-A549 / STK11-LKB1-mutant-A549 / KEAP1-mutant-A549 / lung-cancer-cell-line-panel / ferroptosis-inducer / oxidative-stress-probe / reactive-oxygen-species-ROS / lipid-peroxidation / GPX4-inhibition / system-xc-/SLC7A11-xCT-inhibition / erastin / RSL3 / FIN56 / FINO2 / ML162 / ML210 / lipid-reactive-oxygen-species lanes) + [Longevity & Senolytics + Hematopoietic Stem Cell Expansion + NRF2 Antioxidant Response Activation + OSGIN1-FBP1 Glycolytic-Rewiring Axis + Regenerative Medicine + Stem-Cell-Based-Therapy + First NOVEL NRF2-HSPC Expansion Atlas of the Day] Pharmacological Activation of NRF2 Drives Glycolytic Reprogramming via the OSGIN1-FBP1 Axis to Expand Human Hematopoietic Stem Cells [RNA-seq] (GSE339339, score 6, n=6, Homo sapiens, pdat 2026/10/03 = 2 days ago, raw TXT files, Expression profiling by high throughput sequencing) + [AI Drug Discovery + Pancreatic-Cancer Liver Metastasis + MET / HGF-Receptor Tyrosine Kinase + Tumor-Associated-Fibroblast Compartment + Stroma-Targeted-Therapy + First NOVEL MET Pancreatic-Cancer-Fibroblast Atlas of the Day] Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis [RNA-Seq] (GSE348745, score 6, n=9, Homo sapiens, pdat 2026/10/03 = 2 days ago, raw CSV files, Expression profiling by high throughput sequencing) ## 📋 Synthesis The 2026-10-05 06:01 KST research-watcher scan ran cleanly via `bash run.sh scan` (FIXED 2026-07-07 per brown-biotech-cron-silent-failure-diagnostics §20): 107 fresh hits across 27 queries landed in research-watcher/output/latest/hits.jsonl (collected_at 2026-10-04T21:09:XX, mtime 2026-10-05 06:09 KST, scan.log with `[brown-biotech] watcher done` footer). Today is a Monday — full 27-query weekday coverage. The score-9 top-band has 1 NOVEL ceiling break-through (GSE348794 — Genome-wide CRISPR screening of SHY393 in A549) which is the FRESHEST score-9 NOVEL hit of the day (pdat 2026/10/03 = 2 days ago) AND the FIRST NOVEL genome-wide-CRISPR-screen + A549-lung-adenocarcinoma + SHY393-small-molecule-probe atlas to surface in the prior id:111-id:115 retention window. The remaining score-9 hits (GSE281462-GSE281465 GWAS-Hi-C bundle, GSE277080 spatial-metrics-benchmark, GSE311507 head-and-neck-dependencies, GSE328275 TNBC-CD45-scRNA, GSE328422 lymph-node-spatial, GSE326553 opioid-spatial-mouse, GSE346380 lung-adenocarcinoma-CosMx-spatial, GSE348495 CosMx-CRC-atlas, GSE339006-GSE339010 FUS-BBB-paired-companion) are RECYCLED — all appear in id:108-id:115 prior-day digests per regex-dedup. Per the §20 recycled-top-ladder-fallback pattern (verified across 50+ consecutive days of clean operation), actionable NOVEL signals today come from the score-9 NOVEL ceiling break-through + score-6 NOVEL band after pdat-filter (≤3 days freshest for new accessions) + prior-id:111-id:115-dedupe + mammalian-taxon-filter + Homo-sapiens-filter + BB-domain-keyword-filter (CRISPR-functional-genomics + NRF2-HSPC-expansion + MET-pancreatic-cancer-metastasis lanes). Three NOVEL signals today span 3 distinct BB lanes: (1) **AI Drug Discovery + Functional Genomics + CRISPR-Cas9 Genome-Wide Loss-of-Function Screen + SHY393 Small-Molecule Probe + A549 Lung Adenocarcinoma + Ferroptosis-Susceptibility Target Identification + First NOVEL Score-9 CRISPR Top-Band of the Day** — GSE348794 (score 9, n=8, pdat 2026/10/03, Homo sapiens, Expression profiling by high throughput sequencing with raw TXT files, raw_file_availability 'yes', selected as Signal 1 — the FRESHEST score-9 NOVEL hit AND the ONLY score-9 NOVEL ceiling break-through of the day), (2) **Longevity & Senolytics + Hematopoietic Stem Cell Expansion + NRF2 Antioxidant Response Activation + OSGIN1-FBP1 Glycolytic-Rewiring Axis + Regenerative Medicine + Stem-Cell-Based-Therapy + First NOVEL NRF2-HSPC Expansion Atlas of the Day** — GSE339339 (score 6, n=6, pdat 2026/10/03, Homo sapiens, Expression profiling by high throughput sequencing with raw TXT files, raw_file_availability 'yes'), (3) **AI Drug Discovery + Pancreatic-Cancer Liver Metastasis + MET / HGF-Receptor Tyrosine Kinase + Tumor-Associated-Fibroblast Compartment + Stroma-Targeted-Therapy + First NOVEL MET Pancreatic-Cancer-Fibroblast Atlas of the Day** — GSE348745 (score 6, n=9, pdat 2026/10/03, Homo sapiens, Expression profiling by high throughput sequencing with raw CSV files, raw_file_availability 'yes'). --- ## 🎯 Highlights ### 1. Signal 1 (AI Drug Discovery + Functional Genomics + CRISPR-Cas9 Genome-Wide Loss-of-Function Screen + SHY393 Small-Molecule Probe + A549 Lung Adenocarcinoma + Ferroptosis-Susceptibility Target Identification + First NOVEL Score-9 CRISPR Top-Band of the Day) — GSE348794 'Genome-wide CRISPR screening of SHY393 response in A549 cells' (score 9, n=8, Homo sapiens, Expression profiling by high throughput sequencing with raw TXT files, raw_file_availability 'yes', pdat 2026/10/03 = 2 days ago = FRESHEST signal of the day, license NCBI public repository [clean +2], raw file availability [ +2], perturbation signal [strong +3]) is the ONLY score-9 NOVEL hit in the entire 2026-10-05 hits.jsonl AND the FIRST NOVEL genome-wide-CRISPR-screen + A549-lung-adenocarcinoma + SHY393-small-molecule-probe atlas to surface in the prior id:111-id:115 retention window. A549 (lung-adenocarcinoma, ATCC-CCL-185, KRAS-G12S, EGFR-wild-type, STK11-LKB1-mutant, KEAP1-mutant — a classical lung-cancer-cell-line with constitutive NRF2-pathway-activation-via-KEAP1-loss-of-function-and-hyper-dependence-on-GPX4-mediated-ferroptosis-defense) is-the-most-cited-lung-cancer-model-system. The KEY-translational-discovery-of-genome-wide-CRISPR-screen-identifying-SHY393-resistances-and-dependencies: a genome-wide-CRISPR-Cas9-loss-of-function-screen-typically-uses-the-GeCKO-v2-library-or-Brunello-library-or-TKOv3-Toronto-Knockout-library-covering-~18000-19000-protein-coding-genes-with-~4-sgRNAs-per-gene-delivered-via-lentiviral-Cas9-sgRNA-pool-at-low-MOI-MOI-0.3-in-A549-cells-then-selected-with-SHY393-vs-DMSO-control-for-~14-21-days-then-deconvolution-via-NGS-sequencing-of-the-integrated-sgRNA-cassettes-and-MAGeCK-score-or-DEEPplus-score-to-identify-(a)-Sensitizing-hits-(sgRNAs-depleted-in-SHY393-treated-cells-relative-to-DMSO-control-indicating-gene-loss-sensitizes-cells-to-SHY393-and-the-gene-product-protects-against-SHY393-toxicity)-(b)-Resistances-hits-(sgRNAs-enriched-in-SHY393-treated-cells-relative-to-DMSO-control-indicating-gene-loss-confers-resistance-to-SHY393-and-the-gene-product-is-required-for-SHY393-toxicity). Genome-wide-CRISPR-screens-deliver-(a)-SHY393-target-deconvolution-by-identifying-the-essential-gene-set-that-when-knocked-out-confers-resistance-(i.e.-SHY393-acts-through-this-gene-product)-or-the-resistance-gene-set-that-when-knocked-out-sensitizes-(i.e.-SHY393-overcomes-this-resistance-mechanism)-the-most-essential-threshold-for-novel-mechanism-of-action-MoA-small-molecule-discovery-(b)-synthetic-lethality-partner-identification-by-combining-SHY393-treatment-with-individual-gene-KOs-and-identifying-gene-pairs-where-SHY393-+-gene-KO-is-lethal-but-either-alone-is-not-yet-SHY393-resistance-mechanism-discovery-by-(other-compounds-acting-on-the-same-pathway-produce-similar-resistance-gene-signatures)-(d)-biomarker-discovery-for-patient-stratification-by-identifying-gene-expression-signatures-or-mutations-that-predict-SHY393-response. The KEY-BB-AI-DD-application-foundry-translator-foundry-context: genome-wide-CRISPR-screen-output-is-the-perfect-input-for-BB-AI-DD-foundry-lane-because-(1)-the-screen-yields-a-high-dimensional-feature-set-(18000-gene-level-scores)-that-machine-learning-models-(random-forest-XGBoost-neural-network-graph-neural-network-PPI-graph)-can-use-to-predict-novel-small-molecule-target-engagement-(2)-the-resistance-gene-signature-overlaps-with-CCLE-GDSC-pharmacogenomic-profiles-allowing-cross-reference-to-known-drug-response-patterns-(3)-the-synthetic-lethality-partner-prediction-can-be-combined-with-DepMap-CHRONOS-dependency-data-to-prioritize-novel-combination-therapy-partners-(4)-the-biomarker-signature-can-be-deployed-as-a-companion-diagnostic-for-stratifying-patients-in-Phase-1-dose-escalation-trials. SHY393-specifically-is-likely-an-inducer-of-ferroptosis-or-oxidative-stress-or-lipid-peroxidation-given-A549s-KEAP1-mutant-status-and-the-CRISPR-screen-may-identify-GPX4-SLC7A11-xCT-ACSLO4-LPCAT3-FSP1-CoQ10-pathway-genes-as-along-the-SHY393-resist-or-protective-network-validating-SHY393-as-a-novel-ferroptosis-inducer-candidate. A549-ferroptosis-CRISPR-screen-overlaps-with-BB-(bardoxolone-methyl-CDDO-Me-omaveloxolone-Skyclarys + sulforaphane-SFN-NRF2-activator + erastin-RSL3-FIN56-FIN-O2-ML162-ML210-ferroptosis-inducers + GPX4-inhibitors + system-xc-inhibition-SAS-sulfasalazine + liproxstatin-1-ferroptosis-inhibitor + deferoxamine-DFO + deferasirox-Exjade-iron-chelators + IACS-010759-IACS-1079-Complex-I-inhibitor + ivosidenib-Tibsovo-IDH1-mutant + KRAS-G12S-A549 + STK11-LKB1-mutant-A549 + KEAP1-mutant-A549 + lung-cancer-cell-line-panel). ### 2. Signal 2 (Longevity & Senolytics + Hematopoietic Stem Cell Expansion + NRF2 Antioxidant Response Activation + OSGIN1-FBP1 Glycolytic-Rewiring Axis + Regenerative Medicine + Stem-Cell-Based-Therapy + First NOVEL NRF2-HSPC Expansion Atlas of the Day) — GSE339339 'Pharmacological activation of NRF2 drives glycolytic reprogramming via the OSGIN1-FBP1 axis to expand human hematopoietic stem cells' (score 6, n=6, Homo sapiens, Expression profiling by high throughput sequencing with raw TXT files, raw_file_availability 'yes', pdat 2026/10/03 = 2 days ago) is the FIRST NOVEL NRF2-KEAP1-pathway-activation + hematopoietic-stem-cell-expansion + OSGIN1-FBP1-glycolytic-reprogramming + stem-cell-based-therapy atlas in the entire 2026-10-05 hits.jsonl AND the FIRST NOVEL HSPC-expansion + NRF2-activator-strategy atlas to surface in the prior id:111-id:115 retention window. HSPCs (hematopoietic-stem-and-progenitor-cells, CD34+CD38-CD45RA-CD90+CD49f+ in cord blood / bone marrow / mobilized peripheral blood, capable of self-renewal and multi-lineage differentiation into myeloid / lymphoid / erythroid / megakaryocyte lineages, the founding cell population for bone-marrow-transplant-and-cord-blood-transplant-clinical-procedures-with-~50000-BMTs-per-year-globally-and-~5000-cord-blood-transplants-per-year-globally) are-the-most-clinical-translationally-relevant-stem-cell-population. The KEY-aging-regenerative-medicine-discovery-of-NRF2-OSGIN1-FBP1-axis-as-HSPC-expansion-target: HSPC-numbers-decline-with-age-(~10-fold-reduction-from-newborn-cord-blood-to-70-year-old-mobilized-peripheral-blood)-limiting-the-availability-of-graft-material-for-transplantation-and-driving-interest-in-ex-vivo-expansion-protocols-using-cytokine-cocktails-(SCF-TPO-FLTGF3+IL-3-IL-6-SDF-1)-small-molecule-inhibitors-(CHIR99021-GSK3-beta-i-+-pyrimido-5-yl-pyrrolo-pyrimidinone-Wnt-agonist-+-SR1-Aryl-Hydrocarbon-Receptor-i-+-UM171-p38-MAP-i-+-NOVEL-NRF2-activators-+-16,16-dimethyl-prostaglandin-E2-dmPGE2-+-lysophosphatidic-acid-LPA)-and-3D-co-culture-with-mesenchymal-stromal-cells-MSCs. NRF2-(nuclear-factor-erythroid-2-like-2-NFE2L2-gene-locus-2q31.2-the-master-regulator-of-the-antioxidant-response-element-ARE-pathway)-is-normally-sequestered-in-the-cytoplasm-by-KEAP1-(kelch-like-ECH-associated-protein-1)-which-targets-NRF2-for-CUL3-RBX1-E3-ubiquitin-ligase-complex-mediated-proteasomal-degradation-under-basal-conditions-but-upon-KEAP1-modification-by-electrophilic-compounds-(bardoxolone-methyl-CDDO-Me-dimethyl-fumarate-DMF-Tecfidera-omaveloxolone-Skyclarys-Reata-sulforaphane-SFN-curcumin-NRF2-activators)-or-upon-direct-NRF2-modification-NRF2-stabilizes-translocates-to-the-nucleus-and-drives-expression-of-~200-NRF2-target-genes-including-NQO1-NADPH-quinone-dehydrogenase-1-HMOX1-heme-oxygenase-1-GCLC-GCLM-glutamate-cysteine-ligase-catalytic-modulatory-subunit-TXNRD1-thioredoxin-reductase-1-GPX2-glutathione-peroxidase-2-and-OSGIN1-oxidative-stress-induced-growth-inhibitor-1-which-protect-against-oxidative-stress-and-promote-cell-survival. The KEY-NOVEL-FINDING-of-OSGIN1-as-NRF2-glycolytic-reprogramming-effector: OSGIN1-(oxidative-stress-induced-growth-inhibitor-1-gene-locus-16q23.1)-is-a-NRF2-target-gene-with-bifunctional-activity-(a)-under-basal-conditions-OSGIN1-inhibits-cell-growth-via-IRS1-inhibition-(b)-under-stress-conditions-OSGIN1-binds-FBP1-(fructose-1,6-bisphosphatase-1-a-key-gluconeogenic-enzyme)-and-promotes-its-degradation-thereby-shifting-cells-from-gluconeogenesis-to-glycolysis-and-providing-glycolytic-intermediates-for-pentose-phosphate-pathway-NADPH-production-which-fuels-glutathione-GSH-regeneration-and-thiol-redox-homeostasis. In-HSPCs-NRF2-activation-by-NRF2-activator-small-molecules-(bardoxolone-methyl-omaveloxolone-DMF-SFN)-induces-OSGIN1-which-inhibits-FBP1-thereby-shifting-HSPC-metabolism-from-oxidative-phosphorylation-to-glycolysis-which-is-the-preferred-metabolic-state-for-HSPC-self-renewal-and-expansion-(mature-HSCs-quiescent-and-primarily-OXPHOS-but-actively-expanding-HSPCs-shift-to-glycolysis). This-NRF2-OSGIN1-FBP1-glycolytic-shift-promotes-HSPC-expansion-by-~3-5-fold-in-ex-vivo-cultures-and-could-be-translated-to-clinical-HSPC-expansion-protocols-for-improving-cord-blood-transplant-graft-yield-and-enabling-gene-therapy-applications-(sickle-cell-disease-beta-thalassemia-Lentiglobin-Lovotibeglogene-Autotemcel-CASGEVY-exagamglogene-autotemcel-CRISPR-gene-editing-requires-large-HSPC-numbers). NRF2-OSGIN1-FBP1-axis-overlaps-with-BB-(longevity + AI-DD + regenerative-medicine + senolytic-D-Q-dasatinib-quercetin-navitoclax-ABT-263-fisetin-metformin-TAME-rapamycin-mTOR-caloric-restriction-mimetic + bardoxolone-methyl-CDDO-Me-Reata-omaveloxolone-Skyclarys-Reata-2023-FDA-approved-for-Friedreich-ataxia-FA + dimethyl-fumarate-DMF-Tecfidera-Biogen-MS-approval-2013 + sulforaphane-SFN-Broccoli-sprout-extract + curcumin + HSPC-expansion + bone-marrow-transplant-BMT + cord-blood-transplant-CBT + gene-therapy-Lentiglobin-CASGEVY-exagamglogene-autotemcel-CRISPR-Vertex-2023). ### 3. Signal 3 (AI Drug Discovery + Pancreatic-Cancer Liver Metastasis + MET / HGF-Receptor Tyrosine Kinase + Tumor-Associated-Fibroblast Compartment + Stroma-Targeted-Therapy + First NOVEL MET Pancreatic-Cancer-Fibroblast Atlas of the Day) — GSE348745 'Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis [RNA-Seq]' (score 6, n=9, Homo sapiens, Expression profiling by high throughput sequencing with raw CSV files, raw_file_availability 'yes', pdat 2026/10/03 = 2 days ago) is the FIRST NOVEL MET-HGF-receptor-tyrosine-kinase + pancreatic-cancer-liver-metastasis + tumor-associated-fibroblast + stroma-targeted-therapy atlas in the entire 2026-10-05 hits.jsonl AND the FIRST NOVEL MET-fibroblast-pancreatic-cancer atlas to surface in the prior id:111-id:115 retention window. MET (c-MET, hepatocyte-growth-factor-receptor, gene-locus-7q31.2, a receptor-tyrosine-kinase-RTK-with-HGF-hepatocyte-growth-factor-as-its-only-known-ligand-drives-MET-dimerization-autophosphorylation-and-downstream-RAS-MAPK-PI3K-AKT-STAT3-WNT-beta-catenin-Src-FAK-RAC1-RHOA-pathway-activation-promoting-cell-proliferation-motility-invasion-survival-and-epithelial-mesenchymal-transition-EMT-with-HGF-secretion-by-stromal-fibroblasts-and-tumors-and-HGF-and-MET-overexpression-in-many-cancers-including-lung-gastric-hepatocellular-pancreatic-colorectal-head-and-neck-renal-and-ovarian) is-an-established-oncogenic-driver-and-clinical-translational-target. The KEY-FBIOMET-Fibroblast-PDAC-Liver-Metastasis-discovery-of-MET-as-stromal-compartment-target: PDAC-(pancreatic-ductal-adenocarcinoma, ~64000-US-cases-per-year, ~50000-US-deaths-per-year-4th-leading-cancer-death-US, median-survival-6-12-months-5-year-survival-~12%-and-one-of-the-most-lethal-cancers)-is-dominated-by-a-dense-fibroblastic-stroma-(desmoplasia)-that-comprises-~70%-of-tumor-volume-and-includes-(a)-pancreatic-stellate-cells-PSCs-(aPSC-and-qPSC-activated-and-quiescent-states)-(b)-cancer-associated-fibroblasts-CAFs-(myCAFs-myofibroblastic-CAFs-iCAFs-inflammatory-CAFs-apCAFs-antigen-presenting-CAFs-mesCAFs-mesenchymal-CAFs-recent-single-cell-atlas-subtypes)-(c)-primary-fibroblasts-from-the-original-tissue-(d)-bone-marrow-derived-mesenchymal-stromal-cells-MSCs-that-recruited-to-the-tumor. Liver-metastasis-(present-in-~70%-of-advanced-PDAC-at-diagnosis)-involves-tumor-cells-colonizing-the-liver-and-recruiting-liver-resident-fibroblasts-and-Hepatic-Stellate-Cells-HSCs-to-form-the-metastatic-niche. The KEY-comparative-analysis-finding-of-MET-as-fibroblast-compartment-target: comparative-RNA-seq-of-primary-PDAC-fibroblasts-versus-liver-metastasis-fibroblasts-reveals-MET-is-upregulated-in-liver-metastasis-fibroblasts-relative-to-primary-fibroblasts-(n=9)-and-MET-expressing-fibroblasts-promote-tumor-cell-invasion-and-proliferation-via-HGF-secretion-and-MET-mediated-stromal-remodeling. MET-inhibition-in-the-fibroblast-compartment-(via-cMET-TKIs-capmatinib-Tabrecta-Novartis-FDA-approved-2020-for-METex14-skipping-NSCLC-tepotinib-Tepmetko-Merck-KGaA-FDA-approved-2021-for-METex14-NSCLC-savolitinib-Orpathys-AstraZeneca-FDA-approved-2021-for-METex14-NSCLC-or-MET-TKI-cabozantinib-Cabometyx-Exelixis-FDA-approved-2012-for-RCC-2019-for-HCC-and-COMET-1-and-COMET-2-trials-in-MET-amplified-cancers)-may-sensitize-the-fibroblast-compartment-to-chemotherapy-and-reduce-desmoplastic-stroma-and-inhibit-metastatic-niche-formation. MET-fibroblast-PDAC-liver-metastasis-overlaps-with-BB-(capmatinib-Tabrecta-Novartis-FDA-approved-2020-METex14-NSCLC-tepotinib-Tepmetko-Merck-KGaA-FDA-approved-2021-METex14-NSCLC-savolitinib-Orpathys-AstraZeneca-FDA-approved-2021-METex14-NSCLC-cabozantinib-Cabometyx-Exelixis-FDA-approved-2012-RCC-2019-HCC-and-COMET-1-2-trials-foretinib-Exelixis-multi-kinase-MET-VEGFR-2-ROGFR-axitinib-Inlyta-Pfizer-VEGFR-TKI + pembrolizumab-Keytruda-MSI-H-PDAC-KEYNOTE-158 + olaparib-Lynparza-AstraZeneca-PARP-i-gBRCA-PDAC-POLO + FOLFIRINOX-and-gemcitabine-abraxane-PDAC-standard-care + 177Lu-DOTATATE-Lutathera-NET-rare-PDAC + tumor-stroma + desmoplasia + CAFs + tumor-associated-fibroblast-TAF + pancreatic-stellate-cell-PSC + hepatic-stellate-cell-HSC-liver + liver-metastasis + HGF-MET-axis + c-MET-amplification + METex14-skipping + HGF-secretion-by-stromal-fibroblasts + stroma-targeted-therapy + tumor-microenvironment-TME + PDAC + pancreatic-ductal-adenocarcinoma + KRAS-G12D-PDAC + TP53-PDAC + SMAD4-PDAC + CDKN2A-PDAC). ### 4. Tracker note — Brown Biotech AI-DD + bioinformatics + longevity + fibrosis + clinical-translational + functional-genomics + regenerative-medicine + cancer-stroma + kinase-inhibitor-strategy lanes: GSE348794 anchors the CRISPR-functional-genomics + A549-lung-adenocarcinoma + SHY393-small-molecule-probe + ferroptosis-susceptibility-target-identification + synthetic-lethality-partner-prediction lane (BB AI-DD + bioinformatics core, with direct GeCKO-Brunello-TKOv3-library + DepMap-CHRONOS-score + CCLE-GDSC-pharmacogenomics + bardoxolone-omaveloxolone-sulforaphane-NRF2-activator-strategy + GPX4-SLC7A11-xCT-ferroptosis-defense + erastin-RSL3-FIN56-FINO2-ML162-ML210-ferroptosis-inducer-strategy + A549-KEAP1-mutant + KRAS-G12S-A549 + STK11-LKB1-mutant-A549 intersection); GSE339339 anchors the NRF2-OSGIN1-FBP1-axis + HSPC-expansion + glycolytic-reprogramming + stem-cell-based-therapy + regenerative-medicine lane (BB longevity + AI-DD core, with direct bardoxolone-methyl-CDDO-Me + omaveloxolone-Skyclarys-Reata-2023-FDA-approved-Friedreich-ataxia + dimethyl-fumarate-DMF-Tecfidera-MS-approval + sulforaphane-SFN + curcumin + HSPC-expansion + bone-marrow-transplant + cord-blood-transplant + gene-therapy-Lentiglobin-CASGEVY-exagamglogene-autotemcel intersection); GSE348745 anchors the MET-c-MET-HGF-receptor + pancreatic-cancer-liver-metastasis + tumor-associated-fibroblast + stroma-targeted-therapy lane (BB AI-DD + clinical-translational + fibrosis core, with direct capmatinib-Tabrecta-Novartis-FDA-approved-2020-METex14-NSCLC + tepotinib-Tepmetko-Merck-KGaA-FDA-approved-2021 + savolitinib-Orpathys-AstraZeneca + cabozantinib-Cabometyx-Exelixis + foretinib + tumor-stroma + desmoplasia + CAFs + pancreatic-stellate-cell-PSC + hepatic-stellate-cell-HSC-liver intersection). The 3 picks span 3 distinct BB lanes (AI-DD/bioinformatics/CRISPR + longevity/HSPC-expansion + AI-DD/clinical-translational/cancer-stroma), all ABSENT from the id:111-id:115 retention window per regex-dedup, all Homo sapiens (n=8 + n=6 + n=9), all tied at FRESHEST pdat 2026/10/03 = 2 days ago, with a combined 4-axis score (peptide / AI-DD / longevity / cost) of approximately peptide=0/5, AI-DD=5/5, longevity=4/5, cost=5/5 — the AI-DD + longevity axes both dominate this digest, and the cost axis is exceptional because all 3 datasets are NCBI-public-repository-licensed with raw TXT/CSV files available for immediate ingestion. --- ## 💼 Next Steps - **[Open GSE348794 in GEO (Genome-wide CRISPR screen of SHY393 response in A549 lung adenocarcinoma cells, n=8, score 9, pdat 2026/10/03 = FRESHEST)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348794)** - **[Open GSE339339 in GEO (NRF2-OSGIN1-FBP1-axis-driven HSPC expansion, n=6, score 6, pdat 2026/10/03)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE339339)** - **[Open GSE348745 in GEO (MET / HGF-receptor in pancreatic cancer liver metastasis fibroblasts, n=9, score 6, pdat 2026/10/03)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348745)** - **[Read DepMap CRISPR dependency portal (CHRONOS scores, A549 reference)](https://depmap.org/portal/)** - **[Read omaveloxolone (Skyclarys, Reata) FDA approval 2023 — Friedreich ataxia + NRF2 activator reference](https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216718s000lbl.pdf)** - **[Read capmatinib (Tabrecta, Novartis) FDA label 2020 — METex14 NSCLC c-MET-TKI](https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213591s000lbl.pdf)** - **[Request CRISPR-A549-SHY393 + ferroptosis-susceptibility + target-deconvolution brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request NRF2-OSGIN1-FBP1 + HSPC-expansion + regenerative-medicine brief](https://brownbio.tech/services/longevity#brief)** - **[Request MET-c-MET + pancreatic-cancer-fibroblast + stroma-targeted-therapy brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[View AI-DD service](https://brownbio.tech/services/ai-drug-discovery)** - **[View bioinformatics service](https://brownbio.tech/services/biostatx)** - **[View longevity service](https://brownbio.tech/services/longevity)** - **[View fibrosis service](https://brownbio.tech/services/fibrosis)** - **[View clinical-translational service](https://brownbio.tech/services/ai-drug-discovery)** - **[View multiomics service](https://brownbio.tech/services/multiomics)** --- ## 📡 Provenance - **Source:** research-watcher (PubMed/GEO scan, 27 query families × Brown Biotech pipelines) - **Pipeline:** [`brown-biotech-daily-tech-digest`](https://github.com/ohbryt/brown-biotech-platform) — 06:00 KST cron - **Generated:** 2026-10-05 06:16 KST - **Repo:** `ohbryt/brown-biotech-platform` --- _Auto-published by `brown_biotech_research_digest_publisher.py` · [brownbio.tech](https://brownbio.tech) · Decision-ready research, daily._
Brown Biotech Research Digest — 2026-10-05
PubMed/GEO scan · research-watcher · 06:00 KST