Gotowa bibliografia na temat „Han ye (Ba, Jin)”

The pattern “NP1, NP2 + shi ye”, as found in the Chinese translations of Buddhist texts in the Han Dynasty, is not a direct imitation of, or derivation from, the pattern “NP1, NP2 (Subj) + shi (Pron) ye” of the pre-Qin era. Rather, it comes from the pattern “NP1, NP2 (Predicate N) + shi (Copula)” of the Western Han, Eastern Han, Wei, Jin, and Northern and Southern Dynasties periods. In the Chinese Buddhist translations of the Han Dynasty, “NP1, NP2 + shi” is a variant of “NP1, NP2 + shi ye”. The copious use of the two grammatical patterns in the Chinese translations is not intended to render the sentence-final copula in the original Sanskrit texts. Rather, when narrating stories that tell “the NP1 in the previous existence is in fact the NP2 in the present existence”, the Buddhist writings place a specific emphasis on the NP2 of the present existence. The Predicate NP appearing before the copula in these two patterns serves precisely that purpose. Hence, the use is most suitable for stories of this nature.

Since the 1930s, Chinese archaeologists have discovered a number of inscribed wooden tablets from the early Han to the Western Jin, which were identified as “greeting tablets” of two types, ci 刺 and ye 謁. As attested in transmitted accounts, these tablets played an important role in the communicative etiquette of early imperial and early medieval officialdom; during a meeting ceremony, they were presented by the guest to the host. The present article offers a systematic survey of the available corpus of excavated greeting tablets and explores their wider socio-cultural implications. As a component of the communicative etiquette of the bureaucracy, greeting tablets were instrumental in the adaptation of elements of aristocratic culture to the needs of mass officialdom—a new social stratum that in terms of cultural background differed fundamentally from the hereditary aristocracy of the pre-imperial era but occupied a comparable position as a social and political elite. Depuis les années 1930 les archéologues chinois ont découvert de nombreuses tablettes de bois inscrites datant du début des Han jusqu’aux Jin occidentaux, qui ont été identifiées comme étant des « tablettes de salutation ». Il en existe deux types, les ci 刺 et les ye 謁. Comme l’attestent les textes transmis, ces tablettes jouaient un rôle important dans l’étiquette régissant les communications entre fonctionnaires dans la période impériale ancienne et au début de l’époque médiévale: l’hôte les présentait à l’invité au cours du cérémonial marquant leur rencontre. Cet article propose un inventaire systématique du corpus des tablettes de salutation découvertes dans les fouilles et s’intéresse plus généralement à leurs implications socio-culturelles. Partie intégrante de l’étiquette des communications, ces tablettes ont joué leur rôle dans l’adaptation de certains éléments de la culture aristocratique aux besoins de la masse des fonctionnaires, autrement dit d’un groupe social nouveau dont le fonds culturel différait fondamentalement de celui de l’aristocratie héréditaire mais dont la position en tant qu’élite sociale et politique était comparable.

Baekje showed mature Chinese literature, such as writing poetry and literature using Chinese characters, no different from China, in the Sabi era. And document administration was thoroughly implemented. However, The period of Baekje's acceptance of Chinese characters and administration of documents cannot be specified due to a lack of related historical and archaeological materials, or it tends to be considered too late as the period of King Geunchogo, so I wrote this article to look into it. Baekje's acceptance of Chinese characters was examined through whether and when the Baekje constituent group accepted Chinese characters. Baekje was composed of the ruling class of the Buyeo and Goguryeo migrant groups and the under-dominated class of the Han tribes and Ye tribes. The Baekje ruling group split from Goguryeo, which accepted Chinese characters from the time of its founding and started document administration. The Baekje ruling group also knew about Chinese characters and document administration as the ruling group of Goguryeo at one time. Moreover, the Baekje ruling group established a site in the Han River basin after passing through the Chinese county area, where thorough document administration was implemented. The Baekje ruling group had an understanding of Chinese characters and document administration. In addition, the Han and Ye tribes, which were the dominant class of Baekje, were at the center of the Han River basin, and the Jin and Han societies, which were first located in the Han River basin, also accepted Chinese characters through the influence of Chinese residents and exchanges with Hansa-gun during each period of chaos in Chinese history, and knew or participated in the document administration of Chinese county. Baekje accepted and used Chinese characters from the beginning of its foundation because both the ruling and under-dominated groups of Baekje accepted Chinese characters. Since there was no direct record of the beginning of the administration of documents in Baekje, the beginning of the administration of documents was inferred by reviewing historical facts that presuppose the beginning of the administration of documents in Baekje. The establishment of educational institutions and the compilation of history books took place during the reign of King Geunchogo. In addition, Archaeological materials related to inscriptions from the Hanseong period are generally considered to be from the 4th century or later. This can be said to have begun the administration of documents from the time of King Geuncho's reign, as previous understanding. However, looking at the floor stone of the 道(直) name, the period of implementation of Baekje's ritual system and official ranking system, and diplomatic relations with China and counties, there is room to place the beginning of Baekje's document administration in the reign of King Goi. If we limit the period, Baekje document administration began at least from 260, the 27th year of King Goi's reign, when the official rank system was implemented. If interpreted more positively, document administration may have been implemented from the 7th year of King Goi's reign (240), when the military commander was established and the military authority of the central and local regions was reorganized. The reorganization of central and local military authority was carried out by the military command and control of all Baekje armies. This means unification of military government, and this can only be achieved through clear document administration.

Abstract Abnormal expression and activation of Epidermal Growth Factor Receptor (EGFR) contribute to malignancy development, especially in non-small cell lung cancers (NSCLCs). Although the first- to third-generation EGFR small molecule inhibitors have made significant progress in the treatment of EGFR mutant NSCLC patients, acquired mutations have been developed rapidly, resulting in drug resistance. Targeted protein degradation (TPD) technologies including PROteolysis Targeting Chimeras (PROTACs) have recently emerged as a promising alternative modality to address the confronting issues of small molecule inhibitors such as drug resistance. Recently, we have developed a series of heterobifunctional degraders of EGFR mutant proteins, which showed strong degradation ability against a variety of mutant EGFRs including triple mutants with C797S. DC50 (half-maximal degradation concentrations) values of the degraders were obtained using HiBiT assay in NCI-H1975 (EGFR L858R/T790M), HCC827 (EGFR Del19), and H1299 (EGFR WT) cells. Our lead compounds demonstrated excellent EGFR degradation potency with high selectivity against EGFR wild type. Moreover, C-09045, C-09066, and C-13951 strongly inhibited the cell growth of Ba/F3 cells harboring one of the EGFR mutations including L858R/C797S, Del19/C797S, L858R/T790M/C797S, Del19/T790M/C797S, and Exon20 NPH insertion. By contrast, these compounds showed much weaker potency in normal lung fibroblast (HFL-1) and Ba/F3 cells harboring EGFR wild-type. In PK analysis, C-09066 showed good oral bioavailability in mice (F%=41.4) with desirable pharmacokinetic parameters and robust tumor growth inhibition efficacy in the NCI-H1975 EGFR L858R/T790M/C797S xenograft and the Ba/F3 Del19/C797S allograft mouse models. In summary, we have identified selective, potent, and orally bioavailable degraders of various EGFR mutant proteins with broad spectrum anti-tumor efficacy both in vitro and in vivo. Citation Format: Dong Hyuk Ki, Min Sung Joo, Joonwoo Nam, Hunmi Choi, Kyoungwan Seo, Eun-Jung Kim, Jiyeon Kim, Chulwon Kim, Jimmy Taiguang Jin, Wooseok Han. Discovery of novel heterobifunctional degraders of mutant EGFR proteins for NSCLCs harboring various EGFR mutations. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5006.

Abstract Accurate diagnosis of breast cancer using circulating biomarkers present in plasma remains an important challenge. In particular, protein changes in tumor-derived extracellular vesicles (tdEVs) have emerged as potential biomarkers for breast cancer diagnosis because they accurately reflect dynamic changes in tumors. In this study, we compared the proteomes of extracellular vesicle (EV) isolated from the plasma of 100 breast cancer patients and 30 healthy individuals who visited Severance Hospital between Mar 2010 and Dec 2015. Microfluidic chip-based protocol that facilitates the removal of contaminants such as albumin and immunoglobulins was used for the extraction of enriched tdEVs with small amounts of plasma. Comparative analysis of the proteomes identified 26 significant biomarkers that could indicate differences between breast cancer patients and healthy individuals. Using the LsBoost-CNN-SVM hybrid machine learning algorithm, we especially identified key EV protein biomarkers for detecting triple-negative breast cancer (TNBC), a breast cancer subtype with a poor prognosis and a high recurrence rate, as well as lacking therapeutic and diagnostic targets. Remarkably, a signature consisting of three EV proteins, specifically extracellular matrix protein 1 (ECM1), mannose-binding lectin 2 (MBL2), and biotinidase (BTD), effectively distinguished TNBC patients from healthy individuals. In our proteomic analysis set (n=73), this signature exhibited impressive performance, achieving a sensitivity of 93.3% and specificity of 93% in the accurate discrimination of TNBC from the control group. The validation set (n=40) confirmed these findings, with 100% sensitivity and 80% specificity. This signature not only served as a diagnostic tool but also provided valuable insights into the risk of recurrence and patient prognosis. We found a novel diagnostic approach that holds the potential to revolutionize breast cancer diagnostics by enhancing the reliability of tumor-related information obtained from blood samples. Citation Format: Min Woo Kim, Jee Ye Kim, Young Kim, Suji Lee, Sol Moon, Ju-yong Hyon, Kyung-A Hyun, Yeji Yang, Seongmin Ha, Sunyoung Park, Hogyeong Gawk, Haeji Lee, Eun Hee Han, Jin Young Kim, Hyo-Il Jung, Young-Ho Chung, Seung Il Kim. Integrating machine learning with microfluidic technologies for proteomic profiling of extracellular vesicles in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1843.

Lithium-metal electrodes are of particular interest for next-generation rechargeable batteries because of their high specific capacity and low redox potential. Therefore, Li-metal-based batteries may afford higher energy densities than commercially available Li-ion batteries with graphite anodes. However, various bottlenecks have hampered the commercial development of these batteries, including uncontrolled Li dendrite formation and huge volume changes during cycling. Consequently, Li-metal batteries suffer from low Coulombic efficiency and poor cycling stability. In recent years, there has been extensive research on the design and construction of three-dimensional (3D) porous electrodes that can host metallic Li. However, the low pore utilization and uneven Li plating remain crucial issues. This can be understood in terms of electronic and ionic transport through the framework electrode. The carbon frameworks exhibit high electronic conductance; however, large resistance to Li+ migration in the electrolytes of internal and interparticle pores inhibits the penetration of Li+ deep into the electrode. In this work, we demonstrate that a strong interaction between Li and a lithiophilic nanolayer on a substrate plays a critical role in enhancing pore utilization in carbon framework electrodes. As a model architecture, we examine a Li storage process in a framework electrode consisting of porous carbon derived from metal-organic frameworks (MOFs) and a galvanically displaced Ag layer on a Cu substrate (Cu@Ag). The electrochemical experiments combined with operando XRD measurements and microstructural characterizations suggest that a lithiophilic Ag on the Cu substrate preferentially reacts with Li+ to form Li x Ag during the initial stage of Li plating. This Li x Ag phase acts as a seed that can regulate the subsequent Li plating, promoting confined Li storage in the carbon framework electrode while suppressing top plating. Because of these advantages, the MOF-C framework electrode on Cu@Ag exhibits better cycling stability (>250 cycles) than the MOF-C framework electrode on Cu (140cycles). However, when the thickness of the MOF-C framework is increased to 90 μm, the diffraction peak for Ag remains dominant throughout Li plating-stripping, and the formation of Li x Ag alloys is not clearly detectable in the diffraction patterns, suggesting that only a limited amount of Ag is involved in the alloying reaction with Li+. Based on the computational studies, the efficacy of lithiophilic layers toward improving pore utilization is discussed in terms of the kinetic competition between Li+ transport through porous channels and the interfacial reaction of Li+ with the substrate. This study conveys an important message that the Li-substrate interaction plays a vital role in promoting the confined Li storage; hence, it should be considered a key design factor for porous carbon frameworks with high capacity and long cycle lifetime. References Yun, H. R. Shin, E.-S. Won, H. C. Kang, J.-W. Lee, Confined Li metal storage in porous carbon frameworks promoted by strong Li-substrate interaction, Chem. Eng. J. 430 (2022) 132897. Jin, Y. Ye, Y. Niu, Y. Xu, H. Jin, J. Wang, Z. Sun, A. Cao, X. Wu, Y. Luo, H. Ji, L. J. Wan, Solid-solution-based metal alloy phase for highly reversible lithium metal anode, J. Am. Chem. Soc. 142 (2020) 8818–8826. Kim, J. Lee, J. Yun, S.H. Choi, S.A. Han, J. Moon, J.H. Kim, J.-W. Lee, M.-S. Park, Functionality of dual-phase lithium storage in a porous carbon host for lithium-metal anode, Adv. Funct. Mater. 30 (2020) 1910538.

Abstract RON is a receptor tyrosine kinase of the MET proto-oncogene family, known as macrophage stimulating 1 receptor (MST1R) that recognizes macrophage-stimulating protein (MSP). RON has been known to be highly expressed in several epithelial tumors, promoting tumor progression and metastasis, and on macrophages surface, facilitating M2-like phenotype polarization of tumor-associated macrophages (TAM) to impair anti-tumor functions of CD8+ T cells. Although pharmacological inhibition of RON kinase has received attention from many research groups, monoclonal antibody drug showed a limited clinical efficacy due to RON variant of receptor region. Because the structure homology of kinase domain between RON and MET is 80%, discovery of RON-specific small molecule inhibitor is considered to be highly challenging to achieve. At first, we discovered a lead compound with about 50-fold of RON selectivity against MET kinase. Our medicinal chemistry efforts elevated RON/MET selectivity up to 500~10,000-fold (IC50 = 1~50 nM in RON enzyme assay), and the target specificity was proved through a panel assay of 372 kinases (Reaction Biology Corp.). A series of compounds effectively modulated p-RON and downstream signals (e.g. p-ERK and p-AKT) in MDA-MB-453, and inhibited cell proliferation of Ba/F3 cell-line engineered with human RON kinase. Significant anti-tumor effects were shown in syngeneic mouse models compared to a control group after oral administration, and studies related to immuno-oncology are ongoing in in-vitro or ex-/in-vivo assay systems. In conclusion, we have identified RON selective small molecule inhibitors that will be useful to figure out the biology following RON selective inhibition against MET kinase, and to validate the translational potential of RON kinase as a therapeutic target for human diseases including cancer. Citation Format: Young Jin Ham, GyeongHwan Kim, Juhyun Lee, Jaeyoung Lee, Min Kyung Kim, Sunhong Kim, Woosook Kim, Han Byoul Kim, Sung Woong Jang, Hee Dong Park, Seonguk Jeon, Seok-Joo Kim, Joongheui Cho, Jungjoon Kim, Hong bin Yoon, Youngshin Kwak. Discovery of highly selective RON kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB524.

Abstract Introduction: Bacillus Calmette-Guérin (BCG) is the standard of care for high-risk non-muscle-invasive bladder cancer (NMIBC) following transurethral resection. However, patients often have heterogeneous responses. Even among those who initially respond well to BCG, 10-20% relapse. Identification of reliable biomarkers predicting the efficacy of BCG remains an unmet need. En bloc resection is a novel technique representing a substantial advancement in the surgical management of NMIBC. We sought to investigate genomic and tumor microenvironmental (TME) profiles in NMIBC and explore potential predictive markers for BCG treatment following en-block resection. Methods: A total of 40 patients with high-risk NMIBC (cTis-T1N0M0) were retrospectively enrolled who underwent en bloc resection followed by BCG instillation. Surgical samples were subjected to NGS sequencing using a 520-gene panel (Burning Rock Biotech, Guangzhou) and multiplex immunofluorescence (mIF) assay. Results: The cohort had a median age of 63 years, and 80% were male. After a median follow-up of 21.8 months, 19/40 patients relapsed with a one-year relapse-free survival (RFS) rate of 57.5%. All tumors were microsatellite stable and showed a median TMB of 7.98muts/Mb. Genomic profiling revealed a high prevalence of alterations in TERT (55%), KDM6A (32.5%), KMT2D (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%), KMT2C (25%), and ARID1A (20%). TME analysis showed higher proportions of M1 macrophages and CD56 dim NK cells in the tumoral compartment and more intense infiltration of CD8+ T cells, exhausted CD8+T, CD56 bright NK cells, and M2 macrophages in the stromal compartment. Multivariate analysis identified TERT C228T mutation (HR=3.28 [95%CI:1.225-8.79], p=0.0181) and alteration in KDM6A (HR=2.94 [95%CI:1.040-8.29], p=0.042) as two independent factors associated with inferior RFS. Patients with concomitant TERT C228T and KDM6A alteration had the shortest RFS (median RFS:5.83months) compared with those who were free of (median RFS: NR) or harbored either one of the two alterations (median RFS:9.13months) (p=0.0022). We also found that tumoral infiltration of CD8+T cells was positively associated with RFS (HR=0.29 [95%CI:0.097-0.885], p=0.0208). Conclusion: The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment. Our findings may facilitate the stratification of patients and better guide the clinical decision-making on the management of NMIBC. Citation Format: Qi-Dong Xia, Yao-Bing Chen, Jian-Xuan Sun, Chen-Qian Liu, Jin-Zhou Xu, Zhi-Peng Yao, Ye An, Meng-Yao Xu, Si-Han Zhang, Xing-Yu Zhong, Na Zeng, Si-Yang Ma, Hao-Dong He, Heng-Long Hu, Jia Hu, Yi Lu, Lin Shao, Si-Qi Li, Zheng Liu, Shao-Gang Wang. TERT C228T and KDM6A alterations are potential predictive biomarkers in non-muscle-invasive bladder cancer treated with intravesical Bacillus Calmette-Guérin instillation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2127.

Abstract The use of mitochondrial inhibitors to target oxidative phosphorylation (OXPHOS) in cancer treatment presents a challenge due to dose-limiting toxicities. Moreover, while glycolysis-deficient cancers are vulnerable to OXPHOS inhibition in preclinical models, the full extent of phenotypical and mechanistic consequences of inhibiting OXPHOS in cancers capable of glycolysis is not yet well understood. Our results presented here offer promising insights into potential therapeutic gains from combining p53 restoration strategies with OXPHOS inhibitors, even when applied to glycolysis-competent CRC cells. Treatment with mitochondrial complex I inhibitors did not cause energy stress in CRC cells capable of glycolysis. It does, however, induce DNA replication stress, apparent through an observed cell cycle arrest at the S phase, enrichment of the G2/M DNA-damage checkpoint regulation pathway, and replication fork slowdown. Intriguingly, CRC cells harboring wildtype p53 exhibited more severe replication stress than those carrying mutant p53. Furthermore, siRNA knockdown of p53 attenuates replication stress and reduces cell cycle arrest, underlining the important role of p53 in CRC cell responses to OXPHOS inhibition. Our targeted metabolomics analysis reveals that OXPHOS inhibition results in reductions in the purine nucleotides, adenine monophosphate (AMP) and guanine monophosphate (GMP), as well as the pyrimidine nucleotide, uridine monophosphate (UMP), in CRC cells, regardless of their p53 mutational status. By supplementing cell culture mediums with the purine nucleobases adenine and guanine, and the pyrimidine nucleoside uridine, we observed a partial reversal of the replication fork slowdown and reductions in cell viability. This suggests nucleotide deficiencies are involved in the induction of DNA replication stress caused by OXPHOS inhibition. The nucleotide deficiencies were associated with a decrease in the nucleobase precursor aspartate. By adding aspartate at a supraphysiological concentration, to overcome the low expression of the excitatory amino acid transporter 1 required for cellular import of aspartate, we were able to restore the levels of nucleotides. Collectively, our findings suggest broader potential cancer treatment paradigms via OXPHOS targeting, extending beyond glycolysis-deficient cancers. Our data uncovers that CRC cells, which commonly exhibit the glycolytic phenotype, are susceptible to OXPHOS inhibition, with those carrying wildtype p53 showing heightened sensitivity. Therefore, p53 status could serve as a biomarker for predicting CRC responses to OXPHOS inhibitors. Moreover, our findings suggest that combined strategies of restoring p53 function, using small molecules such as APR-246, might enable reduced dosage of OXPHOS inhibitors in CRC treatment, thereby mitigating their dose-limiting toxicities. Citation Format: Xiao Hong Zhao, Man Man Han, Qian Qian Yan, Yi Meng Yue, Kai Hong Ye, Yuan Yuan Zhang, Liu Teng, Liang Xu, Xiao Jing Shi, Ting La, Yu Chen Feng, Ran Xu, Vinod K. Narayana, David P. De Souza, Tao Liu, Mark Baker, Rick F. Thorne, Xu Dong Zhang, Song Chen, Lei Jin. p53 underpins a dependence on oxidative phosphorylation in glycolysis-competent colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7052.

Abstract Background Previous studies proposed low-pass whole genome sequencing (LP-WGS)-based circulating tumor DNA (ctDNA) analysis as a versatile tool for genomic profiling and therapeutic monitoring of cancer patients. Here we demonstrate LP-WGS ctDNA genomic profiles and its clinical significance in metastatic breast cancer patients. Patients and methods This prospective exploratory study enrolled 207 treatment-naïve metastatic breast cancer patients from Feb 2017 to September 2020 in Yonsei Cancer Center. The median follow-up duration of patients was 35 months. The baseline (n=207) and post-progression (n=48) plasma samples were prospectively collected on first-line systemic therapy, and LP-WGS was employed for ctDNA somatic copy number alteration (CNA) analysis. The CNA burden of ctDNA was scored by “I-score” method, which was developed to measure genome-wide chromosomal instabilities, to be matched with therapy response. The unsupervised molecular clustering and homologous recombination deficiency (HRD) estimation by shallowHRD algorithm were performed using locus-level CNA profiles with 1 mega base pair resolution. Results The baseline I-score ctDNA CNA burden was highest in triple-negative breast cancer (TNBC) patients among subtypes, and the patients were dichotomized by median I-score level 5.54 (range 2.55 to 12.98). The high baseline ctDNA I-score was independently associated with poor overall survival (hazard ratio [HR] = 3.98, p < 0.001) with adjustment of tumor subtype, visceral metastasis, and disease status (de novo stage IV versus recurrent). The progression-free survival (PFS) on endocrine plus CDK4/6 inhibitors (HR = 2.75, p = 0.005), anti-HER2 therapy (HR = 2.52, p = 0.032), and cytotoxic chemotherapy (HR = 2.33, p = 0.012) was also shorter in high baseline I-score patients than in low I-score patients. The locus-level CNA profile was analyzed in high I-score patients (n=103), and the patients were classified into five molecular clusters with distinct overall survival by unsupervised k-means clustering of CNA profile: basal-like, EGFR-high basal-like, CCND1-high, luminal, and HER2-enriched clusters. Patients with BCL6 (p = 0.009) and PIK3CA amplification (p < 0.001) on baseline ctDNA showed significantly shorter PFS on CDK4/6 inhibitor treatment. The matched baseline and post-progression ctDNA analysis found emergence of FGFR1 amplification and MYC amplification after CDK4/6 inhibitor treatment (n=1, each). The ctDNA shallowHRD score was highest in TNBC patients among subtypes, and TNBC patients with high shallowHRD score (≥10) showed high response rate on (58.3% versus 28.6%) on platinum-based chemotherapy. Conclusion LP WGS-based ctDNA analysis provides a robust tool for non-invasive genomic clustering, therapy response prediction, and HRD estimation in metastatic breast cancer patients. All patients (n=207)Low I-score (n=104)High I-score (n=103)N (%)N (%)N (%)Age, Median (Interquartile range)54 (46-62)53 (47-60)54(44-62)GenderFemale205 (99)102 (98.1)103Male2 (1)2 (1.9)0SubtypeHR+ HER2-106 (51.2)61 (58.7)45 (43.7)HR- HER2+33 (15.9)14 (13.5)19 (18.4)HR+ HER2+22 (10.6)11 (10.6)11 (10.7)HR- HER2- (TNBC)46 (22.2)18 (17.3)28 (27.2)Disease statusDe novo stage IV74 (35.7)31 (29.8)43 (41.7)Recurrent133 (64.3)73 (70.2)60 (58.3)Primary therapyEndocrine + CDK 4/6 inhibitor97 (46.9)55 (52.9)42 (40.8)Anti-HER2 based therapy54 (26.1)24 (23.1)30 (29.1)Chemotherapy45 (21.7)16 (15.4)29 (28.2)Others11 (5.3)9 (8.7)2 (1.9)Visceral metastasisYes142 (68.6)60 (57.7)82 (79.6)No65 (31.4)44 (42.3)21 (20.4)Metastasis SitesLung89 (43)43 (41.3)46 (44.7)Brain19 (9.2)4 (3.8)15 (14.6)Liver59 (28.5)13 (12.5)46 (44.7)Bone120 (58)47 (45.2)73 (70.9)Lymph node90 (43.7)32 (30.8)58 (56.9)Pleura33 (15.9)17 (16.3)16 (15.5) Citation Format: Joohyuk Sohn, Min Hwan Kim, Jin Mo Ahn, Won-Ji Ryu, Seul-Gi Kim, Jee Hung Kim, Tae Yeong Kim, Hyun Ju Han, Jee Ye Kim, Hyung Seok Park, Seho Park, Byeong Woo Park, Seung Il Kim, Eun Hae Cho, Gun Min Kim. Whole genome sequencing-based circulating tumor DNA profiling of metastatic breast cancer patients for molecular characterization and therapy response prediction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD6-07.