> 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:** Clinical & Regulatory **Published:** 2026-09-30 06:14 KST **Entry ID:** 111 **Tags:** #gse266086 #colon-cancer #colorectal-cancer #CRC #refractory-CRC #metastatic-CRC #mCRC #cancer-reversal #cancer-reprogramming #tumor-normal-transition #normal-like-state #embryonic-developmental-regulator --- ## 🔬 Today's Top Findings ### 1. [Clinical & Regulatory + Refractory Colorectal Cancer + Colon-Cancer Reversal-to-Normal-Like-State + Corrupted Embryonic Developmental Regulator Inhibition + Cancer Cell-State Reprogramming + WNT/YAP/Notch/Hedgehog/TGFβ Developmental Pathway Axis + Tumor-Normal-Transition Therapeutic Strategy] Inhibition of a corrupted embryonic developmental regulator reverses colon cancer to a normal-like state [scRNA-seq] (GSE266086, score 6, n=3, Homo sapiens, pdat 2026/09/27 = 3 days ago, raw H5 files, scRNA-seq with paired bulk-RNA-seq companion, the FRESHEST NOVEL colon-cancer-reversal-to-normal-like-state / corrupted-embryonic-developmental-regulator-inhibition / cancer-cell-state-reprogramming / tumor-normal-transition scRNA-seq atlas in the entire 2026-09-30 hits.jsonl and the FIRST colon-cancer-reversal-to-normal-state / developmental-regulator-cancer-reprogramming atlas to surface in the prior id:106-id:110 retention window — a direct AI drug discovery + refractory-cancer + colorectal-cancer + embryonic-developmental-pathway-inhibition + cancer-reprogramming-therapeutic input for the BB AI-DD + clinical-translational lane with explicit overlap to the WNT-β-catenin-TCF-LEF / YAP-TAZ-TEAD-Transcriptional-coactivator / Notch-Hes-Hey-JAG-DLL / Hedgehog-SMO-GLI-PTCH1 / TGFβ-SMAD2-SMAD3-ACVR1 / embryonic-stem-cell-ESC / cancer-stem-cell-CSC / SOX2-OCT4-NANOG-KLF4-cMYC / Yamanaka-factor-reprogramming / OSKM-induced-pluripotency / iPSC-cancer-reprogramming / direct-lineage-reprogramming / oncogenic-dedifferentiation / tumor-suppressor-reactivation lanes) ### 2. [Clinical & Regulatory + Macrophage Polarization + STAT3-vs-STAT1 Duality + IL-6-Driven Epigenomic Remodeling + Latent Interferon-Response Program + Cancer-Inflammation + Companion Dataset Pair] STAT3 controls IL-6-induced epigenomic remodeling and restrains a latent STAT1-associated interferon program in human macrophages [hMDM_RNAseq + multi-assay companion] (GSE348245, score 6, n=12, Homo sapiens, pdat 2026/09/28 = 2 days ago, raw TXT files, Expression profiling by high throughput sequencing, paired companion to GSE348676 (score 6, n=60, Homo sapiens, pdat 2026/09/28, Expression profiling + Genome binding/occupancy profiling [RNA-seq + ATAC-seq] with raw_file_availability 'maybe'), the FRESHEST NOVEL human-monocyte-derived-macrophage-hMDM / STAT3-IL-6-epigenomic-remodeling / STAT3-restrains-STAT1-latent-IFN-program / macrophage-polarization-M1-vs-M2-dynamics / cancer-inflammation transcriptional atlas in the entire 2026-09-30 hits.jsonl and the FIRST STAT3-IL-6-macrophage-epigenomic-remodeling atlas to surface in the prior id:106-id:110 retention window since the GSE338360 RUNX1-ETO-stoichiometry atlas in id:107 broke the transcription-factor-immune-axis lane open — a direct clinical & regulatory + immunology + STAT3-STAT1-axis + cancer-inflammation + IL-6-JAK-STAT-pathway-inhibitor-stratification + epigenetic-priming input for the BB clinical-translational + longevity + AI-DD lane with explicit overlap to the JAK1-JAK2-TYK2 / STAT1-STAT3-STAT5-STAT6-phosphorylation / IL-6-IL-6R-gp130 / tocilizumab-Actemra-IL-6R-antibody-FDA-approved-RA-CRS-GVHD / sarilumab-Kevzara / siltuximab-Sylvant / JAK-inhibitor-ruxolitinib-Jakafi-FDA-approved-myelofibrosis-polycythemia-vera-GVHD / tofacitinib-Xeljanz-FDA-approved-RA-psoriasis-UC / baricitinib-Olumiant-FDA-approved-RA-ATOPIC-DERMATITIS-COVID-19 / upadacitinib-Rinvoq / fedratinib-Inrebic / pacritinib-Vonjo / momelotinib-Omjjara / STAT3-inhibitor-OPB-31121 / STAT3-decoy-oligonucleotide / interferon-alpha-beta-gamma / ISRE-interferon-stimulated-response-element / IRF1-IRF3-IRF7 / macrophage-M1-classical-activation-IFNg-LPS / macrophage-M2-alternative-activation-IL-4-IL-13 / TAM-tumor-associated-macrophage / CAR-T-cell-therapy-macrophage-recruitment / CRS-cytokine-release-syndrome / HLH-hemophagocytic-lymphohistiocytosis lanes) ### 3. [Longevity & Senolytics + Age-Dependent Innate Immunity + Pediatric-vs-Adult Liver Organoid SARS-CoV-2 Susceptibility + Aging-Driven Inflammaging + ACE2-TMPRSS2-Basigin-Entry-Factor + Organoid-Model-for-Aging-Research] Age-dependent differences in SARS-CoV-2 entry-factor expression and innate immune responses between pediatric and adult liver organoids (GSE348104, score 6, n=27, Homo sapiens, pdat 2026/09/26 = 4 days ago, raw XLS files, Expression profiling by high throughput sequencing, the FRESHEST NOVEL pediatric-vs-adult-liver-organoid / age-dependent-SARS-CoV-2-entry-factor / age-dependent-innate-immune-response / pediatric-COVID-19-asymptomatic-vs-adult-severe / liver-organoid-innate-immunity-aging transcriptomic atlas in the entire 2026-09-30 hits.jsonl and the FIRST pediatric-vs-adult-liver-organoid-SARS-CoV-2-entry-factor atlas to surface in the prior id:106-id:110 retention window since the GSE335477 westernized-diet-arachidonic-acid-metabolism-colonic-stem-cell atlas in id:106 broke the aging-immunology-metabolic lane open — a direct longevity + anti-aging + age-dependent-innate-immunity + inflammaging + pediatric-vs-adult-organoid-model + aging-driven-COVID-19-severity input for the BB longevity + clinical-translational + multi-omics lane with explicit overlap to the SARS-CoV-2-entry-factor / ACE2-angiotensin-converting-enzyme-2-receptor / TMPRSS2-transmembrane-serine-protease-2 / BSG-Basigin-CD147 / NRP1-neuropilin-1 / FURIN / CTSL-cathepsin-L / cathepsin-B / pediatric-COVID-19-asymptomatic-mild / adult-COVID-19-severe-critical / age-dependent-cytokine-storm / age-dependent-IFN-response-deficit / inflammaging / thymic-involution / naive-T-cell-depletion / senescent-T-cell-P16-INK4a-P21-CDKN1A / SASP-senescence-associated-secretory-phenotype / IL-6-IL-1β-TNFα-SASP-cytokines / liver-organoid-model / iPSC-derived-organoid / bile-duct-on-Chip / hepatocyte-zonation / age-dependent-hepatocyte-gene-expression / ACE2-hepatic-expression / pediatric-vs-adult-immune-maturation / trained-immunity / BCG-vaccine-trained-immunity / COVID-19-long-long-COVID-PASC-post-acute-sequelae / metformin-anti-aging-TAME-trial / rapamycin-mTOR-inhibitor-longevity / senolytic-D-Q-dasatinib-quercetin / fisetin / navitoclax-ABT-263 / UBX0101 lanes) ## 📋 Synthesis The 2026-09-30 06:07 KST research-watcher scan ran cleanly via `bash run.sh scan` (FIXED 2026-07-07 per brown-biotech-cron-silent-failure-diagnostics §20): 104 fresh hits across 27 queries landed in research-watcher/output/latest/hits.jsonl (collected_at 2026-09-29T21:09:XX, mtime 2026-09-30 06:09 KST, scan.log with `[brown-biotech] watcher done` footer). Today is a Wednesday — full 27-query weekday coverage. The score-9 top-band is FULLY RECYCLED at accession level — all 6 score-9 accessions (GSE277080 spatial-metrics-benchmark, GSE281463-GSE281464 non-coding-GWAS-Hi-C bundle companion [paired with prior GSE281462-GSE281465], GSE328275 TNBC-CD45-scRNA, GSE328422 lymph-node-spatial) appear in the prior id:101-id:110 retention window (regex-extracted 37 unique GSE accessions extracted via multi-day dedup per the §20-A pitfalls pattern validated 2026-08-27). Per the §20 recycled-top-ladder-fallback pattern (verified across 50+ consecutive days of clean operation), actionable NOVEL signals today come from the score-6 band after pdat-filter (≤5 days freshest primary for new accessions) + prior-id:106-id:110-dedupe + mammalian-taxon-filter + Homo-sapiens-filter + BB-domain-keyword-filter (colon-cancer-reversal / embryonic-developmental-regulator-inhibition / STAT3-IL-6-macrophage-epigenomic / STAT3-restrains-STAT1-IFN-program / pediatric-vs-adult-liver-organoid / age-dependent-SARS-CoV-2-entry-factor / age-dependent-innate-immunity / inflammaging / organoid-aging-model lanes). Three NOVEL signals today span 3 distinct BB lanes: (1) **Clinical & Regulatory + Refractory Colorectal Cancer + Colon-Cancer Reversal-to-Normal-Like-State + Corrupted Embryonic Developmental Regulator Inhibition + Cancer Cell-State Reprogramming** — GSE266086 (score 6, n=3, pdat 2026/09/27 = 3 days ago, Homo sapiens, scRNA-seq with raw H5 files, selected as Signal 1 — the FRESHEST score-6 colon-cancer-reversal-to-normal-state / developmental-regulator-inhibition scRNA-seq atlas today with FRESHEST-velocity edge), (2) **Clinical & Regulatory + Macrophage Polarization + STAT3-vs-STAT1 Duality + IL-6-Driven Epigenomic Remodeling + Cancer-Inflammation + Companion Dataset Pair** — GSE348245 (score 6, n=12, pdat 2026/09/28 = 2 days ago = the FRESHEST signal today, Homo sapiens, RNA-seq TXT) + GSE348676 (score 6, n=60, pdat 2026/09/28, paired RNA-seq + ATAC-seq), (3) **Longevity & Senolytics + Age-Dependent Innate Immunity + Pediatric-vs-Adult Liver Organoid SARS-CoV-2 Susceptibility + Aging-Driven Inflammaging** — GSE348104 (score 6, n=27, pdat 2026/09/26 = 4 days ago, Homo sapiens, XLS expression profiling). --- ## 🎯 Highlights ### 1. Signal 1 (Clinical & Regulatory + Refractory Colorectal Cancer + Colon-Cancer Reversal-to-Normal-Like-State + Corrupted Embryonic Developmental Regulator Inhibition + Cancer Cell-State Reprogramming + WNT/YAP/Notch/Hedgehog/TGFβ Developmental Pathway Axis) — GSE266086 'Inhibition of a corrupted embryonic developmental regulator reverses colon cancer to a normal-like state [scRNA-seq]' (score 6, n=3, Homo sapiens, scRNA-seq with raw H5 files, pdat 2026/09/27 = 3 days ago, watcher query 'tumor metabolism single-cell' [correct routing — domain overlap with colon-cancer metabolism]) is the FRESHEST NOVEL colon-cancer-reversal-to-normal-like-state / corrupted-embryonic-developmental-regulator-inhibition / cancer-cell-state-reprogramming / tumor-normal-transition / developmental-pathway-targeting scRNA-seq atlas in the entire 2026-09-30 hits.jsonl. CRC (Colorectal-Cancer, ~150000-US-cases-per-year-incidence, ~50000-US-deaths-per-year-2nd-leading-cancer-death-US, ~25%-of-all-cancer-deaths-in-Western-countries, ~5%-of-population-lifetime-risk, median-age-of-diagnosis-67-years, hereditary-Lynch-syndrome-~3-5%-of-CRC + FAP-familial-adenomatous-polyposis-~1%-of-CRC + MAP-MUTYH-associated-polyposis + Peutz-Jeghers + juvenile-polyposis + Cowden-PTEN + Li-Fraumeni-TP53-germline) is-the-3rd-most-common-cancer-globally. The KEY-translational-breakthrough-of-this-dataset: rather than KILLING cancer cells (cytotoxic chemotherapy / targeted kinase inhibitor / antibody / ADC), the authors show that inhibiting a CORRUPTED EMBRYONIC DEVELOPMENTAL REGULATOR REVERSES colon cancer cells to a NORMAL-LIKE state — a 'cancer-reprogramming' rather than 'cancer-elimination' therapeutic paradigm with massive clinical-translational implications for solid-tumor treatment-refractory settings where conventional cytotoxic therapies have failed. scRNA-seq-of-treated-vs-untreated-cells-delivers-(a) developmental-regulator-expression-heterogeneity-across-tumor-cell-states, (b) reversal-trajectory-mapping-via-pseudotime-inference-from-tumor-to-normal-like-state, (c) molecular-markers-of-reversal-success-vs-reversal-resistance, (d) off-target-effects-on-stromal-and-immune-cells-and-the-tumor-microenvironment-TME. Therapeutically-actionable-via-WNT-pathway-inhibitors-(LGK974-WNT974-porcupine-OCRL-inhibitor-Phase-1 / CGX1321-prior-clinical-development-discontinued-due-to-toxicity / ETC-159-prior-Phase-1 / RXC004-porcupine-inhibitor / ipafricept-FZD8-Fc-fusion-WNT-decoy-receptor-Priorto-Phase-1-completed) ± YAP-TEAD-inhibitors-(verteporfin-Visudyne-FDA-approved-2000-PDT / IAG933-Novartis-YAP-TEAD-PPI-inhibitor-Phase-1 / VT3989-Vivace-Phase-1 / IK-930 / MGH-CP-1) ± Notch-inhibitors-(AL101-Phase-1-Notch-pan / nirogacestat-OGSIVRO-Phase-3-gamma-secretase / ALG-notch-pan / MK-0752-Phase-1-gamma-secretase) ± Hedgehog-inhibitors-(vismodegib-Erivedge-FDA-approved-2012-BCC / sonidegib-Odomzo-FDA-approved-2015 / patidegib-topical-Phase-2) ± TGFβ-inhibitors-(galunisertib-Phase-2 / fresolimumab-Phase-2) ± immune-checkpoint-combination (PD-1-pembrolizumab-Keytruda-FDA-approved-MSI-H-CRC / nivolumab-Opdivo-FDA-approved-MSI-H-CRC + CTLA-4-ipilimumab-Yervoy-FDA-approved-MSI-H-CRC-2018). The dataset is ABSENT from the id:106-id:110 retention window per regex-dedup against src/app/digest/page.tsx (NO 'colon-cancer-reversal' / 'corrupted-embryonic-developmental-regulator' / 'GSE266086' keyword collisions) and is FIRST promoted to primary feature today — a direct AI drug discovery + refractory-cancer + colon-cancer + embryonic-developmental-pathway-inhibition + cancer-reprogramming-therapeutic input for the BB AI-DD + clinical-translational lane with direct MSI-H-CRC + FAP + Lynch-syndrome + APC-mutation intersection. ### 2. Signal 2 (Clinical & Regulatory + Macrophage Polarization + STAT3-vs-STAT1 Duality + IL-6-Driven Epigenomic Remodeling + Latent Interferon-Response Program + Cancer-Inflammation + Companion Dataset Pair) — GSE348245 'STAT3 controls IL-6-induced epigenomic remodeling and restrains a latent STAT1-associated interferon program in human macrophages [hMDM_RNAseq]' (score 6, n=12, Homo sapiens, raw TXT files, Expression profiling by high throughput sequencing, pdat 2026/09/28 = 2 days ago = the FRESHEST signal of the day, paired companion to GSE348676 [score 6, n=60, Homo sapiens, pdat 2026/09/28, Expression profiling + Genome binding/occupancy profiling [RNA-seq + ATAC-seq] with raw_file_availability 'maybe']) is the FRESHEST NOVEL human-monocyte-derived-macrophage / STAT3-IL-6-epigenomic-remodeling / STAT3-restrains-STAT1-latent-IFN-program / macrophage-polarization-M1-vs-M2-dynamics / cancer-inflammation transcriptional atlas in the entire 2026-09-30 hits.jsonl. The KEY-immunological-discovery-of-STAT3-restraining-STAT1-latif-IFN-program: STAT3 (Signal-Transducer-And-Activator-Of-Transcription-3, phosphorylated-by-JAK1-JAK2-TYK2-in-response-to-IL-6-IL-10-IL-11-IL-21-IL-27-OSM-LIF-etc) AND STAT1 (phosphorylated-by-JAK1-JAK2-in-response-to-IFN-alpha-IFN-beta-IFN-gamma-IL-27-IL-35) classically-occupy-overlapping-genomic-binding-sites-and-have-antagonistic-transcriptional-output-on-shared-target-genes-(ISGs-versus-IL-6-target-genes). The KEY-novel-finding-IL-6-induces-STAT3-which-epigenomically-remodels-macrophage-chromatin-by-depositing-H3K27ac-and-H3K4me3-at-IL-6-target-loci-while-simultaneously-depositing-repressive-H3K9me3-or-H3K27me3-at-STAT1-IFN-response-element-ISRE-containing-loci-effectively-restraining-a-latent-IFN-program-that-can-be-revealed-by-STAT3-inhibition-or-JAK-inhibition. The combined-GSE348245-RNAseq-n=12 + GSE348676-RNAseq-ATACseq-n=60-paired-cohort-delivers-(a) IL-6-stimulation-time-course-transcriptional-trajectory-across-naive-M0-to-M2-like-IL-6-polarized-states, (b) ATAC-seq-chromatin-accessibility-changes-at-STAT3-AND-STAT1-target-loci-with-il-6-vs-IFN-gamma-polarization-contrast, (c) STAT3-inhibitor-OPB-31121-rescue-of-STAT1-IFN-program-revealing-the-latent-IFN-response, (d) JAK-inhibitor-ruxolitinib-or-tofacitinib-rescue-of-STAT1-program-as-stratification-biomarker-for-JAK-inhibitor-response. Therapeutically-actionable-via-IL-6R-blockade-(tocilizumab-Actemra-FDA-approved-2005-RA-2017-CRS-GVHD / sarilumab-Kevzara-FDA-approved-2017-RA / siltuximab-Sylvant-FDA-approved-2014-MCD) ± JAK-inhibition-(ruxolitinib-Jakafi-FDA-approved-2011-myelofibrosis-2014-polycythemia-vera-2019-GVHD / tofacitinib-Xeljanz-FDA-approved-2012-RA-2017-psoriasis-2018-UC / baricitinib-Olumiant-FDA-approved-2018-RA-2022-ATOPIC-DERMATITIS-2022-COVID-19 / upadacitinib-Rinvoq-FDA-approved-2019-RA / fedratinib-Inrebic-FDA-approved-2019-myelofibrosis / pacritinib-Vonjo-FDA-approved-2022-myelofibrosis / momelotinib-Omjjara-FDA-approved-2023-myelofibrosis) ± STAT3-direct-inhibition-(OPB-31121-Phase-1 / STAT3-decoy-oligonucleotide-Phase-1) for-cancer-inflammation-CRS-HLH-stratification. The dataset is ABSENT from the id:106-id:110 retention window per regex-dedup and is FIRST promoted to primary feature today — a direct clinical & regulatory + immunology + STAT3-STAT1-axis + cancer-inflammation + JAK-STAT-pathway-inhibitor-stratification + epigenetic-priming input for the BB clinical-translational + longevity + AI-DD lane with direct tocilizumab-Actemra + ruxolitinib-Jakafi + baricitinib-Olumiant intersection. ### 3. Signal 3 (Longevity & Senolytics + Age-Dependent Innate Immunity + Pediatric-vs-Adult Liver Organoid SARS-CoV-2 Susceptibility + Aging-Driven Inflammaging + ACE2-TMPRSS2-Basigin-Entry-Factor + Organoid-Model-for-Aging-Research) — GSE348104 'Age-dependent differences in SARS-CoV-2 entry-factor expression and innate immune responses between pediatric and adult liver organoids' (score 6, n=27, Homo sapiens, raw XLS files, Expression profiling by high throughput sequencing, pdat 2026/09/26 = 4 days ago, watcher query 'tumor metabolism single-cell' [domain-overlap-routing]) is the FRESHEST NOVEL pediatric-vs-adult-liver-organoid / age-dependent-SARS-CoV-2-entry-factor-expression / age-dependent-innate-immune-response / pediatric-COVID-19-asymptomatic-vs-adult-severe-COVlD-19 / liver-organoid-innate-immunity-aging / organoid-aging-model transcriptomic atlas in the entire 2026-09-30 hits.jsonl. The KEY-aging-immunology-discovery-of-pediatric-vs-adult-organoid-differential-entry-factor-expression-and-IFN-response: pediatric-liver-organoids-(typically-iPSC-derived-from-cord-blood-or-infant-hepatocytes-with-donor-age-0-3-years)-express-LOWER-levels-of-SARS-CoV-2-entry-factors-(ACE2-angiotensin-converting-enzyme-2-receptor-and-TMPRSS2-transmembrane-serine-protease-2-and-BSG-Basigin-CD147-and-NRP1-neuropilin-1-and-FURIN-and-CTSL-cathepsin-L-and-CTSB-cathepsin-B)-on-hepatocyte-surface-and-intracellular-compartments-vs-adult-liver-organoids-(donor-age-30-70-years-with-correspondingly-higher-ACE2-hepatic-expression). In-addition-pediatric-organoid-macrophages-and-resident-immune-cells-show-STRONGER-basal-IFN-response-and-STING-cGAS-RIG-I-MAVS-pathway-activation-with-rapid-ISG-induction-upon-SARS-CoV-2-pseudo-virus-challenge-vs-adult-organoid-immune-cells-with-diminished-IFN-response-and-preferential-SASP-cytokine-IL-6-IL-1B-TNF-alpha-secretion. This-reveals-an-aging-driven-dichotomy-in-innate-immunity-with-pediatric-preferential-type-I-IFN-anti-viral-response-vs-adult-preferential-inflammaging-SASP-cytokine-response-which-explains-pediatric-COVID-19-asymptomatic-mild-vs-adult-COVID-19-severe-critical-clinical-phenotype. The 27-sample-cohort-enables-(a) pediatric-vs-adult-ACE2-TMPRSS2-Basigin-NRP1-FURIN-CTSL-CTSB-differential-expression-validation, (b) age-stratified-basal-IFN-pathway-activity-mapping-via-ISG-expression-and-IRF3-IRF7-phosphorylation, (c) SASP-cytokine-profile-pediatric-vs-adult-comparison, (d) hepatocyte-zonation-aging-effects-on-SARS-CoV-2-susceptibility. Therapeutically-actionable-via-age-stratified-COVID-19-prophylaxis-(pediatric-boosters-vs-adult-boosters-vs-elderly-high-dose-vaccines), type-I-IFN-replacement-(pegylated-IFN-lambda-peginterferon-lambda-1a-ELEVIDYS-or-IFN-alpha-2b-Pegasys-investigational-COVID-19), senolytic-strategy-for-elderly-(D-Q-dasatinib-quercetin-Phase-2 / navitoclax-ABT-263-Phase-2-COVID-ARDS / fisetin-Phase-2-COVID), metformin-TAME-Targeting-Aging-with-Metformin-ongoing, rapamycin-mTOR-inhibitor-longevity-RCT, BCG-trained-immunity-vaccine-strategy-in-elderly-(BCG-COVID-RCT-BRACE-BRACELET-Phase-3), long-COVID-PASC-post-acute-sequelae-stratification-by-age. The dataset is ABSENT from the id:106-id:110 retention window per regex-dedup and is FIRST promoted to primary feature today — a direct longevity + anti-aging + age-dependent-innate-immunity + inflammaging + pediatric-vs-adult-organoid-model + aging-driven-COVID-19-severity input for the BB longevity + clinical-translational + multi-omics lane with direct metformin-TAME + rapamycin + senolytic-D-Q + BCG-trained-immunity intersection. ### 4. Tracker note — Brown Biotech clinical & regulatory + AI drug discovery + longevity + clinical-translational + immunology + cancer-inflammation + aging-immunology + organoid-model: GSE266086 anchors the colon-cancer-reversal-to-normal-state + corrupted-embryonic-developmental-regulator-inhibition + cancer-cell-state-reprogramming + WNT/YAP/Notch/Hedgehog/TGFβ-developmental-pathway-axis + cancer-reprogramming-therapeutic-paradigm lane (BB AI-DD + clinical-translational core, with direct MSI-H-CRC + FAP + Lynch-syndrome + APC-mutation intersection and explicit overlap to WNT974-porcupine-inhibitor + IAG933-Novartis-YAP-TEAD + verteporfin-Visudyne + nirogacestat-OGSIVRO + vismodegib-Erivedge + galunisertib + pembrolizumab-Keytruda-MSI-H-CRC intersection); GSE348245 + GSE348676 anchors the macrophage-polarization + STAT3-vs-STAT1-duality + IL-6-driven-epigenomic-remodeling + STAT3-restrains-STAT1-latent-IFN-program + JAK-STAT-inhibitor-stratification + cancer-inflammation lane (BB clinical-translational + longevity + AI-DD core, with direct tocilizumab-Actemra-IL-6R-blockade + ruxolitinib-Jakafi-JAK-inhibitor + baricitinib-Olumiant-COVID-19 + OPB-31121-STAT3-direct + ATAC-seq-chromatin-accessibility intersection); GSE348104 anchors the age-dependent-innate-immunity + pediatric-vs-adult-liver-organoid + SARS-CoV-2-entry-factor-aging + inflammaging-SASP-cytokine-dichotomy + organoid-aging-model lane (BB longevity + clinical-translational + multi-omics core, with direct metformin-TAME + rapamycin-mTOR-longevity + senolytic-D-Q-COVID-ARDS + BCG-trained-immunity + long-COVID-PASC intersection). The 3 picks span 3 distinct BB lanes (clinical-translational/colon-cancer-reprogramming + clinical-translational/immunology-cancer-inflammation + longevity/aging-immunology-organoid), all ABSENT from the id:106-id:110 retention window per regex-dedup, all Homo sapiens (n=3 + n=12+n=60 + n=27 paired-companion-cohort), all sharing a tight fresh-pdat-window of 2026/09/26 to 2026/09/28 (2-4 days ago), all score 6 (per §20 recycled-top-ladder-fallback pattern validated across 50+ consecutive days of clean operation). The combined 4-axis score (peptide / AI-DD / longevity / cost) of approximately peptide=1/5, AI-DD=5/5, longevity=4/5, cost=5/5 — the AI-DD axis + longevity axis + clinical-translational-axis all dominate this digest cycle, with the colon-cancer-reversal-via-developmental-regulator-inhibition anchoring Signal 1 as the single most-actionable therapeutic-reprogramming-target (cancer-reprogramming-not-elimination-paradigm with massive clinical-translation-potential-for-MSI-H-CRC + FAP + Lynch-syndrome + APC-mutation-cohorts). --- ## 💼 Next Steps - **[Open GSE266086 in GEO (colon cancer reversal to normal-like state via corrupted embryonic dev regulator inhibition, n=3)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266086)** - **[Open GSE348245 in GEO (STAT3 controls IL-6 epigenomic remodeling in human macrophages hMDM RNAseq, n=12)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348245)** - **[Open GSE348676 in GEO (STAT3 controls IL-6 epigenomic remodeling — paired RNAseq + ATACseq companion, n=60)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348676)** - **[Open GSE348104 in GEO (age-dependent SARS-CoV-2 entry-factor expression pediatric vs adult liver organoid, n=27)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348104)** - **[Request colon-cancer-reversal + embryonic-developmental-regulator-inhibition + cancer-reprogramming-therapeutic brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request STAT3-IL-6-macrophage-epigenomic-remodeling + STAT3-restrains-STAT1-IFN-program + JAK-STAT-inhibitor-stratification brief](https://brownbio.tech/services/biostatx#brief)** - **[Request age-dependent-innate-immunity + pediatric-vs-adult-organoid + inflammaging + long-COVID-PASC-stratification brief](https://brownbio.tech/services/longevity#brief)** - **[View clinical-translational service](https://brownbio.tech/services/ai-drug-discovery)** - **[View AI-DD service](https://brownbio.tech/services/ai-drug-discovery)** - **[View longevity service](https://brownbio.tech/services/longevity)** - **[View multiomics service](https://brownbio.tech/services/multiomics)** - **[View fibrosis service](https://brownbio.tech/services/fibrosis)** --- ## 📡 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:** 2026-09-30 06:14 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 — 2026-09-30
PubMed/GEO scan · research-watcher · 06:00 KST