> 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:** Bioinformatics & Multi-Omics **Published:** 2026-07-01 06:13 KST **Entry ID:** 29 **Tags:** #ESR1 #ESR1-Y537S #estrogen receptor #endocrine resistance #hormonal therapy resistance #ER+ breast cancer #MCF7 #isogenic line #abemaciclib #CDK4/6 inhibitor #CCND1 #cyclin D1 --- ## 🔬 Today's Top Findings ### 1. Transcriptomic profiling of MCF7 ESR1-PARENT and ESR1-Y537S cells cultured under estrogen-depleted or estradiol-supplemented conditions following abemaciclib treatment and CCND1 knockdown (GSE336731, score 9, n=36, Homo sapiens, pdat 2026/06/29) ### 2. Single-cell RNA sequencing of CD45+ immune cells across primary tumor, sentinel tumor-draining lymph node, and axillary lymph node in treatment-naive triple-negative breast cancer (GSE328275, score 9, n=28, Homo sapiens, pdat 2026/06/27) ### 3. Independent cell type-specific expression and distal regulation of the 9p21 locus cell cycle regulators: p14ARF, p16INK4A, p15INK4A, and ANRIL [CRISPR and scRNA-seq] (GSE309511, score 9, n=32, Homo sapiens, pdat 2026/06/29) ## 📋 Synthesis Three fresh score-9 high-impact hits spanning AI drug discovery / oncology hormonal-resistance perturbation (estrogen-depleted vs estradiol-supplemented MCF7 ESR1-PARENT vs ESR1-Y537S isogenic-line transcriptomics after abemaciclib + CCND1-knockdown combination treatment — the cleanest possible ESR1 / cell-cycle dual-perturbation design for ER+ breast cancer endocrine-resistance dissection), bioinformatics / spatial-immunology TNBC tumor-draining-LN atlas (treatment-naive triple-negative breast cancer single-cell RNA-seq of CD45+ immune cells across primary tumor + sentinel tumor-draining LN + axillary LN — the cleanest possible matched-anatomical three-region immune atlas for understanding TNBC immune-draining trajectories at single-cell resolution), and longevity / senolytics 9p21 cell-cycle-regulator CRISPR screen (cell type-specific expression + distal CRISPR-based regulation dissection of the p14ARF / p16INK4A / p15INK4A / ANRIL 9p21 cell-cycle regulators — p16INK4A is THE canonical senescence marker and a central aging biomarker; ANRIL is the long non-coding RNA that scaffolds CDKN2A/B regulatory architecture and a GWAS hit for cardiovascular disease, type 2 diabetes, and multiple cancers), drawn from the research-watcher's 2026-07-01 scan (collected_at 2026-06-30T21:02–21:03 UTC = 2026-07-01 06:02–06:03 KST; 105 hits ingested in the latest/ output directory; ~71 unique non-digested accessions after de-duplicating against id:25–id:28): (1) Transcriptomic profiling of MCF7 ESR1-PARENT and ESR1-Y537S cells cultured under estrogen-depleted or estradiol-supplemented conditions following abemaciclib treatment and CCND1 knockdown (GSE336731, score 9, n=36, pdat 2026/06/29, RNA-seq perturbation, Homo sapiens, clean license, raw files available, suppfile CSV) — a freshly deposited (pdat = 2 days ago) score-9 ESR1 isogenic-line transcriptomic dissection of MCF7 (ER+ breast cancer) under estrogen-depleted vs estradiol-supplemented conditions with abemaciclib (CDK4/6 inhibitor, the standard-of-care first-line therapy for ER+/HER2− metastatic breast cancer) + CCND1 (cyclin D1, the G1/S cell-cycle checkpoint driver and direct pharmacological target of CDK4/6 inhibition) knockdown combination treatment; the ESR1-PARENT vs ESR1-Y537S isogenic-line comparison is the gold-standard design for ESR1-activating-mutation resistance dissection (ESR1-Y537S is the most common constitutively-active ligand-independent ESR1 mutation driving ∼30–40% of metastatic ER+ breast cancer endocrine-therapy resistance) and the abemaciclib + CCND1-knockdown dual perturbation is the cleanest possible dissection of whether CCND1 amplification / overexpression is the dominant CDK4/6 inhibitor resistance mechanism; this is the most actionable MCF7 combination-perturbation dataset in today's scan and a direct AI drug discovery input for Brown Biotech's oncology / ER+ breast cancer endocrine-resistance lane (where second-line ESR1-mutant-selective degraders like vepdegestrant received FDA approval in 2024–2025); the n=36 cohort supports well-powered differential analysis across estrogen-condition × ESR1-genotype × treatment × knockdown-strategy combinations; pairs conceptually with the GSE326226 Xenium muscle-invasive bladder cancer lineage-vulnerability atlas (id:28) and the GSE311507 HNSCC subtype-specific dependency atlas (id:25) on a shared breast / oncology precision-targeting thread. (2) Single-cell RNA sequencing of CD45+ immune cells across primary tumor, sentinel tumor-draining lymph node, and axillary lymph node in treatment-naive triple-negative breast cancer (GSE328275, score 9, n=28, pdat 2026/06/27, single-cell + spatial, Homo sapiens, clean license, raw-file availability maybe flagged, suppfile not declared) — a freshly deposited (pdat = 4 days ago) score-9 matched-anatomical-three-region CD45+ immune-cell single-cell atlas across primary tumor + sentinel tumor-draining lymph node (the first LN to receive lymphatic drainage from the tumor and a critical staging biopsy site) + axillary lymph node (the downstream-most standard-of-care staging LN for breast cancer staging) in treatment-naive triple-negative breast cancer (TNBC, the most aggressive breast cancer subtype with 5-year survival <30% for advanced disease and limited response to immune checkpoint blockade); this is the cleanest possible matched-three-region single-cell design for understanding TNBC immune-draining trajectories at single-cell resolution and a direct bioinformatics / spatial-immunology input for Brown Biotech's TNBC lymph-node-metastasis lane (axillary LN status remains the single most important prognostic factor in TNBC and a major determinant of treatment intensification); the n=28 sample structure across the three matched anatomical regions delivers the maximum-utility immune-dissection design; pairs with the GSE328422 spatio-temporal immune-cell dynamics lymph-node-metastasis atlas (today, below the fold) on a shared TNBC lymph-node-metastasis thread. (3) Independent cell type-specific expression and distal regulation of the 9p21 locus cell cycle regulators: p14ARF, p16INK4A, p15INK4A, and ANRIL [CRISPR and scRNA-seq] (GSE309511, score 9, n=32, pdat 2026/06/29, single-cell + CRISPR, Homo sapiens, clean license, raw files available, suppfile MTX/TSV) — a freshly deposited (pdat = 2 days ago) score-9 cell type-specific expression + distal CRISPR-based regulation dissection of the 9p21 locus cell-cycle regulators (p14ARF / p16INK4A / p15INK4A from the CDKN2A/CDKN2B locus, the canonical senescence + cell-cycle brake genes; ANRIL = CDKN2B-AS1, the antisense long non-coding RNA that scaffolds the locus and is itself a GWAS hit for cardiovascular disease, type 2 diabetes, and multiple cancers); p16INK4A (CDKN2A-isoform-1) is THE canonical senescence marker used in every major senescence atlas and a direct longevity biomarker; this is the cleanest possible cell-type-specific + distal-regulatory dissection of the 9p21 locus and a direct longevity / senolytics + cell-type-specific-perturbation input for Brown Biotech's aging biology and senescence-target nomination lane (cellular senescence accumulation is a central aging hallmark and an active therapeutic target for senolytics and senostatics); the n=32 cohort supports well-powered cell-type-stratified analysis paired with CRISPR perturbation dissecting the 9p21 distal regulatory architecture; pairs with the IL-17A myocarditis atlas / Skeletal muscle NMJ atlas / Rapamycin fly atlas / Photoaged-skin JAK-STAT atlas / Aged muscle-stem-cell epigenetic atlas / IGF2 sarcopenia atlas / GDF15 sarcopenia atlas (today, below the fold) on a shared longevity / aging-muscle + senescence biology thread. --- ## 🎯 Highlights ### 1. GSE336731 — ESR1-Y537S isogenic-line abemaciclib + CCND1-knockdown (GSE336731, score 9, n=36, pdat 2026/06/29, RNA-seq perturbation, Homo sapiens, clean license, raw files available, suppfile CSV): freshly deposited (pdat = 2 days ago) score-9 ESR1 isogenic-line transcriptomic dissection of MCF7 (ER+ breast cancer) under estrogen-depleted vs estradiol-supplemented conditions with abemaciclib (CDK4/6 inhibitor, the standard-of-care first-line therapy for ER+/HER2− metastatic breast cancer) + CCND1 (cyclin D1, G1/S checkpoint driver and direct pharmacological target of CDK4/6 inhibition) knockdown combination treatment — the gold-standard ESR1-PARENT vs ESR1-Y537S isogenic-line design is the canonical approach for ESR1-activating-mutation resistance dissection (ESR1-Y537S is the most common constitutively-active ligand-independent ESR1 mutation driving ∼30–40% of metastatic ER+ breast cancer endocrine-therapy resistance) and the abemaciclib + CCND1-knockdown dual perturbation is the cleanest possible dissection of whether CCND1 amplification / overexpression is the dominant CDK4/6 inhibitor resistance mechanism; direct AI drug discovery input for Brown Biotech's oncology / ER+ breast cancer endocrine-resistance lane (where second-line ESR1-mutant-selective degraders like vepdegestrant received FDA approval in 2024–2025); the n=36 cohort supports well-powered differential analysis across estrogen-condition × ESR1-genotype × treatment × knockdown-strategy combinations; pairs conceptually with the GSE326226 Xenium muscle-invasive bladder cancer lineage-vulnerability atlas (id:28) and the GSE311507 HNSCC subtype-specific dependency atlas (id:25) on a shared breast / oncology precision-targeting thread. ### 2. Single-cell RNA sequencing of CD45+ immune cells across primary tumor, sentinel tumor-draining lymph node, and axillary lymph node in treatment-naive triple-negative breast cancer (GSE328275, score 9, n=28, pdat 2026/06/27, single-cell + spatial, Homo sapiens, clean license, raw-file availability maybe flagged, suppfile not declared): freshly deposited (pdat = 4 days ago) score-9 matched-anatomical-three-region CD45+ immune-cell single-cell atlas across primary tumor + sentinel tumor-draining lymph node (the first LN to receive lymphatic drainage from the tumor and a critical staging biopsy site) + axillary lymph node (the downstream-most standard-of-care staging LN for breast cancer) in treatment-naive triple-negative breast cancer (TNBC, the most aggressive breast cancer subtype with 5-year survival <30% for advanced disease and limited response to immune checkpoint blockade) — the gold-standard matched-three-region single-cell design for understanding TNBC immune-draining trajectories at single-cell resolution and a direct bioinformatics / spatial-immunology input for Brown Biotech's TNBC lymph-node-metastasis lane (axillary LN status remains the single most important prognostic factor in TNBC and a major determinant of treatment intensification); the n=28 sample structure across the three matched anatomical regions delivers the maximum-utility immune-dissection design; pairs with the GSE328422 spatio-temporal immune-cell dynamics lymph-node-metastasis atlas (today, below the fold) on a shared TNBC lymph-node-metastasis thread. ### 3. Independent cell type-specific expression and distal regulation of the 9p21 locus cell cycle regulators: p14ARF, p16INK4A, p15INK4A, and ANRIL [CRISPR and scRNA-seq] (GSE309511, score 9, n=32, pdat 2026/06/29, single-cell + CRISPR, Homo sapiens, clean license, raw files available, suppfile MTX/TSV): freshly deposited (pdat = 2 days ago) score-9 cell type-specific expression + distal CRISPR-based regulation dissection of the 9p21 locus cell-cycle regulators (p14ARF / p16INK4A / p15INK4A from the CDKN2A/CDKN2B locus, the canonical senescence + cell-cycle brake genes; ANRIL = CDKN2B-AS1, the antisense long non-coding RNA that scaffolds the locus and is itself a GWAS hit for cardiovascular disease, type 2 diabetes, and multiple cancers) — p16INK4A (CDKN2A-isoform-1) is THE canonical senescence marker used in every major senescence atlas and a direct longevity biomarker; the cleanest possible cell-type-specific + distal-regulatory dissection of the 9p21 locus and a direct longevity / senolytics + cell-type-specific-perturbation input for Brown Biotech's aging biology and senescence-target nomination lane (cellular senescence accumulation is a central aging hallmark and an active therapeutic target for senolytics and senostatics); the n=32 cohort supports well-powered cell-type-stratified analysis paired with CRISPR perturbation dissecting the 9p21 distal regulatory architecture; pairs with the IL-17A myocarditis atlas / Skeletal muscle NMJ atlas / Rapamycin fly atlas / Photoaged-skin JAK-STAT atlas / Aged muscle-stem-cell epigenetic atlas / IGF2 sarcopenia atlas / GDF15 sarcopenia atlas (today, below the fold) on a shared longevity / aging-muscle + senescence biology thread. ### 4. Combined signal: AI drug discovery / oncology hormonal-resistance perturbation (ESR1-Y537S isogenic-line MCF7 transcriptomics with abemaciclib + CCND1-knockdown dual perturbation dissecting CCND1-mediated CDK4/6 inhibitor resistance in ER+ breast cancer) + bioinformatics / spatial-immunology TNBC atlas (matched-anatomical-three-region CD45+ immune-cell single-cell atlas across primary tumor + sentinel + axillary LN in treatment-naive TNBC) + longevity / senolytics 9p21 locus CRISPR + scRNA-seq (cell-type-specific expression + distal CRISPR-based regulation dissection of p14ARF / p16INK4A / p15INK4A / ANRIL with the canonical senescence marker p16INK4A as the central longevity biomarker) — three orthogonal modalities spanning 3 of 6 Brown Biotech coverage categories (AI drug discovery, bioinformatics, longevity), all clean-license GEO with raw files available (one with raw-file-availability maybe-flagged) and all freshly deposited within the last 4 days; the watcher's 2026-07-01 scan (collected_at 2026-06-30T21:02–21:03 UTC = 2026-07-01 06:02–06:03 KST) ran on its normal 06:00 KST cadence and emitted 105 hits (∼71 unique non-digested accessions after de-duplicating against id:25–id:28); today's three picks emphasize fresh-deposition data (all 3 within 4 days) over the older methodology-atlas picks (GSE277080, GSE308146-48, GSE299886/GSE300007) that have anchored recent digests, with the IL-17A myocarditis / Skeletal muscle NMJ / Rapamycin fly / Photoaged-skin JAK-STAT / Aged muscle-stem-cell epigenetic / IGF2 sarcopenia / GDF15 sarcopenia longevity channel (score-4 GEO + HF) and the GSE328422 spatio-temporal TNBC LN-metastasis atlas reinforcing today's picks below the fold. --- ## 💼 Next Steps - **[Request AI drug discovery / ER+ ESR1-CCND1 abemaciclib-resistance brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request bioinformatics / TNBC triple-region immune-atlas brief](https://brownbio.tech/multiomics#brief)** - **[Request longevity / 9p21 CDKN2A p16INK4A senescence brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[View biostatx service](https://brownbio.tech/services/biostatx)** --- ## 📡 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:** 2026-07-01 06:13 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 — 2026-07-01
PubMed/GEO scan · research-watcher · 06:00 KST