bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and performance of an adaptive adfreeze pile
Authors: Oswell James M. , Coutts Ron
Published: May 2024

Field studies and geothermal modelling show ground cooling below raised buildings in permafrost regions significantly offsets the ground warming impact of climate warming. For an adfreeze pile, the ground cooling below a raised building improves the capacity relative to pre-construction conditions. Many designers do not take credit for this cooling effect but propose to incorporate thermal mitigation in the design, such as the use of thermopiles. The adaptive adfreeze pile is an innovative concept that accounts for long-term cooling beneath raised buildings and the resulting enhanced pile capacity. The concept entails the installation of a closed ended steel pipe as a conventional adfreeze pile. If future ground temperatures warm above a design-specified threshold, a small diameter thermosyphon could be inserted into the interior of the hollow pile. The retrofitted thermosyphon, if ever required, would passively cool the ground during winter to reduce the mean annual ground temperature and maintain pile capacity. This approach is cost-effective compared to conventional thermopile design and provides greater thermosyphon performance assurances in the long-term. This paper details the application of this pile design for two multi-story buildings in Old Crow Yukon, and describes the geothermal background showing its technical feasibility and initial performance data.
Drops of volatile binary mixtures on brush-covered substrates
Authors: Diekmann Jan , Thiele Uwe
Published: May 2024

We introduce a mesoscopic hydrodynamic model for drops of binary mixtures of volatile partially wetting liquids on brush-covered substrates, i.e., we model the coupled dynamics of spreading, evaporation, imbibition, diffusion and partial demixing of the two volatile components across the three phases—brush, drop and gas. The formulation of the model as gradient dynamics on an underlying free energy functional allows us to systematically account for cross-couplings between the six scalar fields needed to describe the dynamics of both components within each of the three phases. The energy accounts for concentration- and brush state-dependent capillarity and wettability, miscibility of the two components within drop and brush, and entropy in the gas. Finally, the usage of the model is illustrated by employing numerical time simulations to study the dynamics of a sessile drop.
Intra-plate Jal Az-Zor strike-slip faulting deciphering the enigma of local earthquakes in Kuwait
Authors: Al-Helal Anwar B. , Al-Mahmoud Mohammed J.
Published: May 2024

Kuwait National Seismic Network (KNSN) data show the clustering of earthquakes in northern and southern clusters. Spatial correlation between these clusters and oil fields led previous studies to declare that oil production/injection triggered earthquakes, but some suggested the possibility of tectonic causes.

This study addresses the genuine objective of uncovering the origin of Kuwait earthquakes by analysing relationships between earthquake spatial and temporal patterns, oil production/injection, structural and tectonic setting, and subsurface fluid pressures.

A kinematic model of the Jal Az-Zor dextral-slip fault was presented as a decipherer to the earthquake's origin. The northern and southern clusters represent leading quadrants, where increased mean stress causes earthquakes. Dibdibah Trough and Kuwait Bay represent trailing quadrants with decreased mean stress and a lack of earthquakes. The small percentage of earthquakes falling outside clusters are caused by the concentration of regional compressive stresses related to Arabian Plate motion on pre-existing faults. Triggering earthquakes by oil field operations requires 10% pressure increase above the original pressures, which never occurs in Kuwait oil fields.

The results of this study emphasize the significance of understanding fault kinematics to assess earthquake hazards and the need to focus on engineering requirements for developments in the leading quadrants areas.
Electrodeposition of Ru on Nanoscale Trench Patterns
Authors: Kim Y. , Lee J. , Seo J. , Han H. , Hwang I. , Yoon S. , Yoo B.
Published: May 2024

Ru deposition in advanced technology nodes can improve performance by providing low resistance in nanoscale features. In this study, we reported the electrochemical reactions of Ru3+ on an Ru surface using multi-cyclic voltammetry (CV) and behavior of additives during Ru electrodeposition using linear sweep voltammetry (LSV) and potentiostatic measurements. Disodium 3,3’-dithiobis(1-propanesulfonate) (SPS), polyvinylpyrrolidone (PVP), and a bromide ion (Br−) were added for bottom-up filling. We investigated the suppression behavior of PVP. The current density and the onset potential of suppressor breakdown were affected by the suppressor concentration. PVP interacted synergistically with Br− and showed additional suppression. PVP formed a suppressing layer with Br− after formation of a bromide layer. SPS could reduce roughness during electrodeposition of Ru. Based on these results, nano-trenches were filled with Ru using the optimized additive condition.
Enhancing flow-mediated dilation analysis by optimizing an open-source software with automated edge detection
Authors: Masterova Kseniya S. , Wang Jiefei , Mack Courtney , Moro Tatiana , Deer Rachel , Volpi Elena
Published: May 2024

This study improves edge detection capabilities and implements noise reduction strategies to optimize an existing open-source software’s suitability for flow-mediated dilation (FMD) analysis. The modified software improves the precision and reliability of FMD analysis compared with the original software algorithm. We demonstrate that this modified open-source software is a robust tool for FMD analysis.
Investigating the Relationship between Smoking and Panic Disorder: A Cross-Sectional Study among US Adults
Authors: Shafiee Arman , Goodarzi Mana , Firouzabadi Shahryar Rajai , Mohammadi Ida , Sadeghi Dina , Zarei Mehrshad , Abdollahi Abolfazl , Kolahdooz Ali , Bakhtiyari Mahmood
Published: May 2024

Background. Previous research on panic risk factors within the US population has been limited. This cross-sectional study is aimed at exploring the association between smoking and panic among adults in the United States. Methods. We conducted an analysis of data from the National Health and Nutrition Examination Survey. Results. The study included 2,222 participants. Those diagnosed with panic disorder were more likely to be female, unmarried, have lower income, engage in higher rates of smoking, and exhibit greater alcohol consumption. Participants who smoke cigarettes occasionally indicated a significant increase in panic disorder (unadjusted OR 95% CI: 4.396 [2.032-9.513]; P<0.001). The significance of our results remained even after performing the multivariate analysis (full-adjusted OR 95% CI: 2.89 [1.30-6.42]). Furthermore, participants who never smoked cigarettes demonstrated strong and significantly low odds for panic disorder, regardless of adjustment (unadjusted OR 95% CI: 0.180 [0.055-0.591]). There was no association between pipe and cigar smoking and panic disorder in both unadjusted and full-adjusted models. Conclusion. This study highlights that smoking remains a significant risk factor for panic disorder, even after accounting for potential confounding variables. Further prospective longitudinal research should be done to investigate the causality between smoking and panic disorder.
Supplementary Figures and Tables Legends from Chromoplexy Is a Frequent Early Clonal Event in EWSR1-Rearranged Round Cell Sarcomas That Can Be Detected Using Clinically Validated Targeted Sequencing Panels
Authors: Dermawan Josephine K. , Slotkin Emily , Tap William D. , Meyers Paul , Wexler Leonard , Healey John , Vanoli Fabio , Vanderbilt Chad M. , Antonescu Cristina R.
Published: May 2024

Supplementary Figures and Tables Legends
Supplementary Figures S1-S12 from Chromoplexy Is a Frequent Early Clonal Event in EWSR1-Rearranged Round Cell Sarcomas That Can Be Detected Using Clinically Validated Targeted Sequencing Panels
Authors: Dermawan Josephine K. , Slotkin Emily , Tap William D. , Meyers Paul , Wexler Leonard , Healey John , Vanoli Fabio , Vanderbilt Chad M. , Antonescu Cristina R.
Published: May 2024

Figure S1. gGraphs depicting gWalk showing connectivities of chromoplectic structural variants (each represented by different color paths) to common nodes.
Figure S2. Circos plots depicting the canonical and noncanonical structural variants detected in prostate carcinoma cases with TMPRSS2::ERG driver fusion.
Figure S3. Inter- vs. intrachromosomal chromooplectic events among cases with EWSR1::FLI1, EWSR1::ERG or EWSR1::WT1 driver fusions.
Figure S4. Longitudinal sequencing of sequential Ewing sarcoma (EWSR1::FLI1) cases illustrating structural variants, gene-level mutations and copy number variations, and arm-level chromosomal gains and losses.
Figure S5. Longitudinal sequencing of sequential desmoplastic small round cell tumor (EWSR1::WT1) cases illustrating structural variants, gene-level mutations and copy number variations, and arm-level chromosomal gains and losses.
Figure S6. Distribution of age among cases with EWSR1::FLI1, EWSR1::ERG or EWSR1::WT1 with or without chromoplexy.
Figure S7. Heatmap and boxplot quantifying percentage genome with copy number variations among cases with EWSR1::FLI1, EWSR1::ERG or EWSR1::WT1 with or without chromoplexy.
Figure S8. Frequency of chr8 gains among cases with EWSR1::FLI1, EWSR1::ERG or EWSR1::WT1 with or without chromoplexy.
Figure S9. Kaplan-Meier curves for overall and progression-free survival in Ewing sarcoma with EWSR1::FLI1 versus EWSR1::ERG.
Figure S10. Kaplan-Meier curves for overall and progression-free survival in Ewing sarcoma with or without chromoplexy.
Figure S11. Kaplan-Meier curves for overall and progression-free survival in desmoplastic small round cell tumor with or without chromoplexy.
Figure S12. Kaplan-Meier curves for overall and progression-free survival in all Ewing sarcoma cases with or without chr8 gains.
Supplementary Data 1 from Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors
Authors: Magrath Justin W. , Sampath Shruthi Sanjitha , Flinchum Dane A. , Hartono Alifiani B. , Goldberg Ilon N. , Boehling Julia R. , Savkovic Suzana D. , Lee Sean B.
Published: May 2024

EWSR1::WT1 Upregulated Pathways
CRDC Program Collaborator Names from NCI Cancer Research Data Commons: Cloud-Based Analytic Resources
Authors: Pot David , Worman Zelia , Baumann Alexander , Pathak Shirish , Beck Rowan , Beck Erin , Thayer Katherine , Davidsen Tanja M. , Kim Erika , Davis-Dusenbery Brandi , Otridge John , Pihl Todd , Barnholtz-Sloan Jill S. , Kerlavage Anthony R.
Published: May 2024

Contributing author list corresponding to "the CRDC Program" which is listed as an author.
Supplementary Table S4. from MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer
Authors: Zheng Si Min , Feng Yu Chen , Zhu Qin , Li Ruo Qi , Yan Qian Qian , Teng Liu , Yue Yi Meng , Han Man Man , Ye Kaihong , Zhang Sheng Nan , Qi Teng Fei , Tang Cai Xia , Zhao Xiao Hong , Zhang Yuan Yuan , Xu Liang , Xu Ran , Xing Jun , Baker Mark , Liu Tao , Thorne Rick F. , Jin Lei , Preiss Thomas , Zhang Xu Dong , Cang Shundong , Gao Jin Nan
Published: May 2024

List of siRNAs/shRNAs.
Supplementary Table S2. from MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer
Authors: Zheng Si Min , Feng Yu Chen , Zhu Qin , Li Ruo Qi , Yan Qian Qian , Teng Liu , Yue Yi Meng , Han Man Man , Ye Kaihong , Zhang Sheng Nan , Qi Teng Fei , Tang Cai Xia , Zhao Xiao Hong , Zhang Yuan Yuan , Xu Liang , Xu Ran , Xing Jun , Baker Mark , Liu Tao , Thorne Rick F. , Jin Lei , Preiss Thomas , Zhang Xu Dong , Cang Shundong , Gao Jin Nan
Published: May 2024

List of antibodies.
Supplementary Table S1. from MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer
Authors: Zheng Si Min , Feng Yu Chen , Zhu Qin , Li Ruo Qi , Yan Qian Qian , Teng Liu , Yue Yi Meng , Han Man Man , Ye Kaihong , Zhang Sheng Nan , Qi Teng Fei , Tang Cai Xia , Zhao Xiao Hong , Zhang Yuan Yuan , Xu Liang , Xu Ran , Xing Jun , Baker Mark , Liu Tao , Thorne Rick F. , Jin Lei , Preiss Thomas , Zhang Xu Dong , Cang Shundong , Gao Jin Nan
Published: May 2024

List of cell lines.
Supplementary Fig. S6. from MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer
Authors: Zheng Si Min , Feng Yu Chen , Zhu Qin , Li Ruo Qi , Yan Qian Qian , Teng Liu , Yue Yi Meng , Han Man Man , Ye Kaihong , Zhang Sheng Nan , Qi Teng Fei , Tang Cai Xia , Zhao Xiao Hong , Zhang Yuan Yuan , Xu Liang , Xu Ran , Xing Jun , Baker Mark , Liu Tao , Thorne Rick F. , Jin Lei , Preiss Thomas , Zhang Xu Dong , Cang Shundong , Gao Jin Nan
Published: May 2024

MILIP interacts with type II tRNAs, tRNA(Leu) and tRNA(Ser).
Table S13 from Proteogenomic Characterization Reveals Estrogen Signaling as a Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR or ALK Alterations
Authors: Park Seung-Jin , Ju Shinyeong , Goh Sung-Ho , Yoon Byoung-Ha , Park Jong-Lyul , Kim Jeong-Hwan , Lee Seonjeong , Lee Sang-Jin , Kwon Yumi , Lee Wonyeop , Park Kyung Chan , Lee Geon Kook , Park Seog Yun , Kim Sunshin , Kim Seon-Young , Han Ji-Youn , Lee Cheolju
Published: May 2024

Table S13
Supplementary Fig. S4. from MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer
Authors: Zheng Si Min , Feng Yu Chen , Zhu Qin , Li Ruo Qi , Yan Qian Qian , Teng Liu , Yue Yi Meng , Han Man Man , Ye Kaihong , Zhang Sheng Nan , Qi Teng Fei , Tang Cai Xia , Zhao Xiao Hong , Zhang Yuan Yuan , Xu Liang , Xu Ran , Xing Jun , Baker Mark , Liu Tao , Thorne Rick F. , Jin Lei , Preiss Thomas , Zhang Xu Dong , Cang Shundong , Gao Jin Nan
Published: May 2024

MILIP promotes nascent protein production.
Supplementary Fig. S3. from MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer
Authors: Zheng Si Min , Feng Yu Chen , Zhu Qin , Li Ruo Qi , Yan Qian Qian , Teng Liu , Yue Yi Meng , Han Man Man , Ye Kaihong , Zhang Sheng Nan , Qi Teng Fei , Tang Cai Xia , Zhao Xiao Hong , Zhang Yuan Yuan , Xu Liang , Xu Ran , Xing Jun , Baker Mark , Liu Tao , Thorne Rick F. , Jin Lei , Preiss Thomas , Zhang Xu Dong , Cang Shundong , Gao Jin Nan
Published: May 2024

MILIP does not bind to mutant p53 in TNBC, whereas there are distinct amino acid sequences in eEF1a1 compared with the corresponding regions in eEF1a2.
Supplementary Fig. S2. from MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer
Authors: Zheng Si Min , Feng Yu Chen , Zhu Qin , Li Ruo Qi , Yan Qian Qian , Teng Liu , Yue Yi Meng , Han Man Man , Ye Kaihong , Zhang Sheng Nan , Qi Teng Fei , Tang Cai Xia , Zhao Xiao Hong , Zhang Yuan Yuan , Xu Liang , Xu Ran , Xing Jun , Baker Mark , Liu Tao , Thorne Rick F. , Jin Lei , Preiss Thomas , Zhang Xu Dong , Cang Shundong , Gao Jin Nan
Published: May 2024

c-Myc transactivates MILIP in TNBC.
Figure S1 from NCI Cancer Research Data Commons: Lessons Learned and Future State
Authors: Kim Erika , Davidsen Tanja , Davis-Dusenbery Brandi N , Baumann Alexander , Maggio Angela , Chen Zhaoyi , Meerzaman Daoud , Casas-Silva Esmeralda , Pot David , Pihl Todd , Otridge John , Shalley Eve , Barnholtz-Sloan Jill S. , Kerlavage Anthony R.
Published: May 2024

Cancer Research Data Commons (CRDC) displaying each component of the CRDC infrastructure.
Supplementary Methods and Figures from Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial–Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma
Authors: Guinn Samantha , Kinny-Köster Benedict , Tandurella Joseph A. , Mitchell Jacob T. , Sidiropoulos Dimitrios N. , Loth Melanie , Lyman Melissa R. , Pucsek Alexandra B. , Zabransky Daniel J. , Lee Jae W. , Kartalia Emma , Ramani Mili , Seppälä Toni T. , Cherry Christopher , Suri Reecha , Zlomke Haley , Patel Jignasha , He Jin , Wolfgang Christopher L. , Yu Jun , Zheng Lei , Ryan David P. , Ting David T. , Kimmelman Alec , Gupta Anuj , Danilova Ludmila , Elisseeff Jennifer H. , Wood Laura D. , Stein-O'Brien Genevieve , Kagohara Luciane T. , Jaffee Elizabeth M. , Burkhart Richard A. , Fertig Elana J. , Zimmerman Jacquelyn W.
Published: May 2024

Supplementary methods and figures
Supplemental Table 3: Pattern 7 Ordered Genes from Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial–Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma
Authors: Guinn Samantha , Kinny-Köster Benedict , Tandurella Joseph A. , Mitchell Jacob T. , Sidiropoulos Dimitrios N. , Loth Melanie , Lyman Melissa R. , Pucsek Alexandra B. , Zabransky Daniel J. , Lee Jae W. , Kartalia Emma , Ramani Mili , Seppälä Toni T. , Cherry Christopher , Suri Reecha , Zlomke Haley , Patel Jignasha , He Jin , Wolfgang Christopher L. , Yu Jun , Zheng Lei , Ryan David P. , Ting David T. , Kimmelman Alec , Gupta Anuj , Danilova Ludmila , Elisseeff Jennifer H. , Wood Laura D. , Stein-O'Brien Genevieve , Kagohara Luciane T. , Jaffee Elizabeth M. , Burkhart Richard A. , Fertig Elana J. , Zimmerman Jacquelyn W.
Published: May 2024

Pattern_7_ordered_genes
Supplemental Table 1: Pancreas Gene Markers from Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial–Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma
Authors: Guinn Samantha , Kinny-Köster Benedict , Tandurella Joseph A. , Mitchell Jacob T. , Sidiropoulos Dimitrios N. , Loth Melanie , Lyman Melissa R. , Pucsek Alexandra B. , Zabransky Daniel J. , Lee Jae W. , Kartalia Emma , Ramani Mili , Seppälä Toni T. , Cherry Christopher , Suri Reecha , Zlomke Haley , Patel Jignasha , He Jin , Wolfgang Christopher L. , Yu Jun , Zheng Lei , Ryan David P. , Ting David T. , Kimmelman Alec , Gupta Anuj , Danilova Ludmila , Elisseeff Jennifer H. , Wood Laura D. , Stein-O'Brien Genevieve , Kagohara Luciane T. , Jaffee Elizabeth M. , Burkhart Richard A. , Fertig Elana J. , Zimmerman Jacquelyn W.
Published: May 2024

Pancreas Gene Markers
Supplementary table 7 from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

Supplementary Table NO. 7
Supplementary discussion from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

supplementary discussion
Supplementary Figure 7 from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

Additional analysis of missense variants near the GSK3β domain
Supplementary Figure 5 from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

Comparison of overexpressed and endogenous levels of AXIN1 mRNA.
Supplementary Figure 3 from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

Analysis of evolutionary conserved AXIN1 residues using the ConSurf tool.
Supplementary Figure 2 from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

Analysis of the AXIN1 mutational landscape
Supplementary Figure 11 from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

Deleting part of the RGS/APC domain at endogenous levels results in increased β-catenin signaling
Supplementary Figure 10 from Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Zhang Ruyi , Li Shanshan , Schippers Kelly , Li Yunlong , Eimers Boaz , Lavrijsen Marla , Wang Ling , Cui Guofei , Chen Xin , Peppelenbosch Maikel P. , Lebbink Joyce H.G. , Smits Ron
Published: May 2024

An accurate removal of the RGS/APC binding domain is required to correctly determine the functional consequences of losing this domain
Data from Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors
Authors: Magrath Justin W. , Sampath Shruthi Sanjitha , Flinchum Dane A. , Hartono Alifiani B. , Goldberg Ilon N. , Boehling Julia R. , Savkovic Suzana D. , Lee Sean B.
Published: May 2024

Abstract
Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to a 5-year survival rate of only 15% to 25%. Here, we depleted EWSR1::WT1 in DSRCT and established its essentiality in vivo. Transcriptomic analysis revealed that EWSR1::WT1 induces unique transcriptional alterations compared with WT1 and other fusion oncoproteins and that EWSR1::WT1 binding directly mediates gene upregulation. The E-KTS isoform of EWSR1::WT1 played a dominant role in transcription, and it bound to the CCND1 promoter and stimulated DSRCT growth through the cyclin D–CDK4/6–RB axis. Treatment with the CDK4/6 inhibitor palbociclib successfully reduced growth in two DSRCT xenograft models. As palbociclib has been approved by the FDA for the treatment of breast cancer, these findings demonstrate the sensitivity of DSRCT to palbociclib and support immediate clinical investigation of palbociclib for treating this aggressive pediatric cancer.
Significance:
EWSR1::WT1 is essential for desmoplastic small round cell tumors and upregulates the cyclin D–CDK4/6–RB axis that can be targeted with palbociclib, providing a targeted therapeutic strategy for treating this deadly tumor type.
Data from NCI Cancer Research Data Commons: Cloud-Based Analytic Resources
Authors: Pot David , Worman Zelia , Baumann Alexander , Pathak Shirish , Beck Rowan , Beck Erin , Thayer Katherine , Davidsen Tanja M. , Kim Erika , Davis-Dusenbery Brandi , Otridge John , Pihl Todd , Barnholtz-Sloan Jill S. , Kerlavage Anthony R.
Published: May 2024

Abstract
The NCI's Cloud Resources (CR) are the analytical components of the Cancer Research Data Commons (CRDC) ecosystem. This review describes how the three CRs (Broad Institute FireCloud, Institute for Systems Biology Cancer Gateway in the Cloud, and Seven Bridges Cancer Genomics Cloud) provide access and availability to large, cloud-hosted, multimodal cancer datasets, as well as offer tools and workspaces for performing data analysis where the data resides, without download or storage. In addition, users can upload their own data and tools into their workspaces, allowing researchers to create custom analysis workflows and integrate CRDC-hosted data with their own.

See related articles by Brady et al., p. 1384, Wang et al., p. 1388, and Kim et al., p. 1404
Hold the MYCrophone: MYC Invades Enhancers to Control Cancer-Type Gene Programs
Authors: MacPherson-Hawthorne Kevin , Sears Rosalie C.
Published: May 2024

MYC is an oncogenic transcription factor that binds gene promoters to facilitate oncogenic gene expression. When overexpressed, as is the case in most human cancers, MYC also invades active enhancers—cis-regulatory elements that are critical for regulating gene expression. In previous studies, the regulatory significance of MYC enhancer invasion in cancer cells has been debated. In their study published in Nature Genetics, Jakobsen and colleagues establish a new role for MYC in enhancer regions: regulating cancer type–specific gene programs. Their work reveals a mechanism in which MYC cooperates with other oncogenic transcription factors to recruit epigenetic regulators to enhancers, resulting in an epigenetic “switch” that promotes enhancer activation through BRD4 and RNA polymerase II. This activity was highly cancer-type specific, highlighting gene expression programs that predicted clinical outcome in a subtype-specific manner in patients with breast cancer.
Table S2 from Evaluating for Correlations between Specific Metabolites in Patients Receiving First-Line or Second-Line Immunotherapy for Metastatic or Recurrent NSCLC: An Exploratory Study Based on Two Cohorts
Authors: Xu Yanjun , Ding Kaibo , Peng Zhongsheng , Ding Ling , Li Hui , Fan Yun
Published: May 2024

Table S2: The TOP10 up- or-down* regulated metabolics in Cohort 1.
Table S1 from Evaluating for Correlations between Specific Metabolites in Patients Receiving First-Line or Second-Line Immunotherapy for Metastatic or Recurrent NSCLC: An Exploratory Study Based on Two Cohorts
Authors: Xu Yanjun , Ding Kaibo , Peng Zhongsheng , Ding Ling , Li Hui , Fan Yun
Published: May 2024

Table S1: Patient demographics and baseline clinicopathological characteristics.
Supplementary Figure S2 from Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates
Authors: Petersen Mark E. , Brant Michael G. , Lasalle Manuel , Das Samir , Duan Renee , Wong Jodi , Ding Tong , Wu Kaylee J. , Siddappa Dayananda , Fang Chen , Zhang Wen , Wu Alex M. L. , Hirkala-Schaefer Truman , Garnett Graham A. E. , Fung Vincent , Yang Luying , Hernandez Rojas Andrea , Lawn Samuel O. , Barnscher Stuart D. , Rich Jamie R. , Colombo Raffaele
Published: May 2024

Supplementary Figure S2 shows the chemical stability of FD1 (ZD06519)
Table S6 from Pharmacological Characterization of SDX-7320/Evexomostat: A Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-tumor and Anti-metastatic Activity
Authors: Cornelius Peter , Mayes Benjamin A. , Petersen John S. , Turnquist David J. , Dufour Pierre J. , Dannenberg Andrew J. , Shanahan James M. , Carver Bradley J.
Published: May 2024

Levels of small molecule MetAP2 inhibitors SDX-7539 and TNP-470 in plasma and CSF, used to assess CNS penetration.
Table S3 from Pharmacological Characterization of SDX-7320/Evexomostat: A Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-tumor and Anti-metastatic Activity
Authors: Cornelius Peter , Mayes Benjamin A. , Petersen John S. , Turnquist David J. , Dufour Pierre J. , Dannenberg Andrew J. , Shanahan James M. , Carver Bradley J.
Published: May 2024

Results of competition for radioligand binding by SDX-9402 at different receptors, to assess the selectivity of the MetAP2 inhibitor against known drug targets.
Figure S2 from Pharmacological Characterization of SDX-7320/Evexomostat: A Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-tumor and Anti-metastatic Activity
Authors: Cornelius Peter , Mayes Benjamin A. , Petersen John S. , Turnquist David J. , Dufour Pierre J. , Dannenberg Andrew J. , Shanahan James M. , Carver Bradley J.
Published: May 2024

Shows binding assay performance and differential MetAP2 binding of test compounds.
Supplementary Figure S3 from The Antipsychotic Drug Penfluridol Inhibits N-Linked Glycoprotein Processing and Enhances T-cell–Mediated Tumor Immunity
Authors: Xu Wenlong , Wang Yuqi , Zhang Na , Lin Xiaofeng , Zhu Di , Shen Cheng , Wang Xiaobo , Li Haiyang , Xue Jinjiang , Yu Qian , Lu Xinyi , Zhou Lu , He Qingli , Tang Zhijun , He Shaodan , Fan Jianjun , Pan Jianbo , Tang Jiangjiang , Jiang Wei , Ye Mingliang , Lu Fanghui , Li Zengxia , Dang Yongjun
Published: May 2024

(a) The stability of proteins was determined by cellular thermal shift at different concentrations of penfluridol.
Supplementary Table 1 from Darolutamide Added to Docetaxel Augments Antitumor Effect in Models of Prostate Cancer through Cell Cycle Arrest at the G1–S Transition
Authors: Buck Stefan A.J. , Van Hemelryk Annelies , de Ridder Corrina , Stuurman Debra , Erkens-Schulze Sigrun , van ’t Geloof Sem , Teubel Wilma J. , Koolen Stijn L.W. , Martens-Uzunova Elena S. , van Royen Martin E. , de Wit Ronald , Mathijssen Ron H.J. , van Weerden Wytske M.
Published: May 2024

Oligo sequences
Supplementary Figure S2 from The Antipsychotic Drug Penfluridol Inhibits N-Linked Glycoprotein Processing and Enhances T-cell–Mediated Tumor Immunity
Authors: Xu Wenlong , Wang Yuqi , Zhang Na , Lin Xiaofeng , Zhu Di , Shen Cheng , Wang Xiaobo , Li Haiyang , Xue Jinjiang , Yu Qian , Lu Xinyi , Zhou Lu , He Qingli , Tang Zhijun , He Shaodan , Fan Jianjun , Pan Jianbo , Tang Jiangjiang , Jiang Wei , Ye Mingliang , Lu Fanghui , Li Zengxia , Dang Yongjun
Published: May 2024

(a) qPCR analysis of the GRP78 and CHOP expression in MDA-MB-231 cells after the treatment with the indicated concentrations for 6 hours.
(b) Western blot analysis of Integrin β1 expression pattern in MDA-MB-231 cells after indicated drugs treatment for 24 hours.
(c) Western blot analysis of protein expression pattern of Integrin β1 in MDA-MB-231 cells treated with the indicated siRNA.
Figure S2 from Darolutamide Added to Docetaxel Augments Antitumor Effect in Models of Prostate Cancer through Cell Cycle Arrest at the G1–S Transition
Authors: Buck Stefan A.J. , Van Hemelryk Annelies , de Ridder Corrina , Stuurman Debra , Erkens-Schulze Sigrun , van ’t Geloof Sem , Teubel Wilma J. , Koolen Stijn L.W. , Martens-Uzunova Elena S. , van Royen Martin E. , de Wit Ronald , Mathijssen Ron H.J. , van Weerden Wytske M.
Published: May 2024

Combination of docetaxel and darolutamide in PC346C-Enzalutamide resistant cells.
A: Dose-response curve with mean normalized viability (+/- SEM) of three separate experiments with technical sextuplicates. Curves were interpolated by non-linear regression analysis and used to determine absolute IC50 value.
Figure S1 from Darolutamide Added to Docetaxel Augments Antitumor Effect in Models of Prostate Cancer through Cell Cycle Arrest at the G1–S Transition
Authors: Buck Stefan A.J. , Van Hemelryk Annelies , de Ridder Corrina , Stuurman Debra , Erkens-Schulze Sigrun , van ’t Geloof Sem , Teubel Wilma J. , Koolen Stijn L.W. , Martens-Uzunova Elena S. , van Royen Martin E. , de Wit Ronald , Mathijssen Ron H.J. , van Weerden Wytske M.
Published: May 2024

Combination of docetaxel and darolutamide in VCaP PDXOs
A: Dose-response curve with mean normalized viability (+/- SEM) of three separate experiments with technical sextuplicates. Curves were interpolated by non-linear regression analysis and used to determine absolute IC50 value.
B: Logarithmic Combination Index (CI) plot for the combination of docetaxel and darolutamide, identifying synergistic (log(CI) < 0), additive (log(CI) = 0) or antagonistic (log(CI) > 0) effects. Fa: fractional effect. The combination index and corresponding degree of synergism or antagonism is indicated for each combination.(18)
Table S3 from 4′-Ethynyl-2′-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress
Authors: Calbert Marissa L. , Chandramouly Gurushankar , Adams Clare M. , Saez-Ayala Magali , Kent Tatiana , Tyagi Mrityunjay , Ayyadevara V.S.S. Abhinav , Wang Yifan , Krais John J. , Gordon John , Atkins Jessica , Toma Monika M. , Betzi Stéphane , Boghossian Andrew S. , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Goldman Aaron R. , Gorman Nicole , Mitra Ramkrishna , Childers Wayne E. , Graña Xavier , Skorski Tomasz , Johnson Neil , Hurtz Christian , Morelli Xavier , Eischen Christine M. , Pomerantz Richard T.
Published: May 2024

ADME and PK properties of 1µM EdC in vitro.
Table S2 from 4′-Ethynyl-2′-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress
Authors: Calbert Marissa L. , Chandramouly Gurushankar , Adams Clare M. , Saez-Ayala Magali , Kent Tatiana , Tyagi Mrityunjay , Ayyadevara V.S.S. Abhinav , Wang Yifan , Krais John J. , Gordon John , Atkins Jessica , Toma Monika M. , Betzi Stéphane , Boghossian Andrew S. , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Goldman Aaron R. , Gorman Nicole , Mitra Ramkrishna , Childers Wayne E. , Graña Xavier , Skorski Tomasz , Johnson Neil , Hurtz Christian , Morelli Xavier , Eischen Christine M. , Pomerantz Richard T.
Published: May 2024

Data collection and refinement statistics of the dCK/UDP/EdC crystal structure.
Supplementary Table S3 from Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models
Authors: Ma Weijie , Wei Sixi , Li Qianping , Zeng Jie , Xiao Wenwu , Zhou Chihong , Yoneda Ken Y. , Zeki Amir A. , Li Tianhong
Published: May 2024

Supplementary Table S3
Supplementary Fig S6 from Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models
Authors: Ma Weijie , Wei Sixi , Li Qianping , Zeng Jie , Xiao Wenwu , Zhou Chihong , Yoneda Ken Y. , Zeki Amir A. , Li Tianhong
Published: May 2024

Supplemental Fig S6
Data from Momordicine-I Suppresses Head and Neck Cancer Growth by Reprogrammimg Immunosuppressive Effect of the Tumor-Infiltrating Macrophages and B Lymphocytes
Authors: Sur Subhayan , Bhartiya Pradeep , Steele Robert , Brennan Michelle , DiPaolo Richard J. , Ray Ratna B.
Published: May 2024

Abstract
Head and neck cancer (HNC) is prevalent worldwide, and treatment options are limited. Momordicine-I (M-I), a natural component from bitter melon, shows antitumor activity against these cancers, but its mechanism of action, especially in the tumor microenvironment (TME), remains unclear. In this study, we establish that M-I reduces HNC tumor growth in two different immunocompetent mouse models using MOC2 and SCC VII cells. We demonstrate that the anticancer activity results from modulating several molecules in the monocyte/macrophage clusters in CD45+ populations in MOC2 tumors by single-cell RNA sequencing. Tumor-associated macrophages (TAM) often pose a barrier to antitumor effects, but following M-I treatment, we observe a significant reduction in the expression of Sfln4, a myeloid cell differentiation factor, and Cxcl3, a neutrophil chemoattractant, in the monocyte/macrophage populations. We further find that the macrophages must be in close contact with the tumor cells to inhibit Sfln4 and Cxcl3, suggesting that these TAMs are impacted by M-I treatment. Coculturing macrophages with tumor cells shows inhibition of Agr1 expression following M-I treatment, which is indicative of switching from M2 to M1 phenotype. Furthermore, the total B-cell population in M-I-treated tumors is significantly lower, whereas spleen cells also show similar results when cocultured with MOC2 cells. M-I treatment also inhibits PD1, PD-L1, and FoxP3 expression in tumors. Collectively, these results uncover the potential mechanism of M-I by modulating immune cells, and this new insight can help to develop M-I as a promising candidate to treat HNCs, either alone or as adjuvant therapy.
Abstract ED03-01: Breaking the Obesity-Breast Cancer Link: Comparing Diet, Drug and Surgical Approaches
Authors: Hursting S.
Published: May 2024

The prevalence of obesity, an established risk and progression factor for at least 15 types of cancer (including breast cancer), continues to rise in the US and many other countries. Lifestyle approaches to weight loss have proven challenging for most people to maintain, and bariatric surgery, while effective, is expensive and has numerous adverse effects. The recent availability of highly effective incretin therapies for weight loss raises several key questions that we will address, including: i) do these agents drive weight loss in obese female mice?; ii) do they reverse obesity-induced metabolic dysregulation?; iii) can they reverse obesity-driven cancer?; iv) how heterogeneous is the response to these agents? We will report our study of the effects of extended (13 weeks) tirzepatide (TZP, a dual GLP1R/GIPR agonist) treatment in obese female mice on weight loss, metabolic hormones, and mammary tumor growth. We found that—similar to reports in the literature using male mice—obese female mice lost >20% body weight by 4 weeks of TZP treatment. Moreover, TZP-induced weight loss was maintained through 13 weeks of treatment by progressively escalating the dose up to 40 nmol/kg. Congruent with reports in male rodents and humans, we found the majority of weight loss in female mice was attributed to loss of adipose tissue, rather than lean mass. The effects of TZP on body weight and composition were associated with reversal of obesity-induced changes in glycemic control and circulating levels of metabolic hormones, particularly leptin, insulin, and IGF-1. TZP also significantly reversed the protumor effects of obesity in our murine E0771 orthotopic transplant model of TNBC.Furthermore, daily 30% calorie restriction, which we previously reported has strong weight loss-inducing, metabolic reprogramming and anticancer effects in multiple mouse models of breast and other cancers, reversed body weight, adiposity, and TNBC tumor growth and altered metabolic hormones to a greater extent than all groups studied, including the never-obese control mice and TZP-treated mice.

Citation Format: S. Hursting. Breaking the Obesity-Breast Cancer Link: Comparing Diet, Drug and Surgical Approaches [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED03-01.
Abstract ED03-02: Mechanisms for the effects of incretin and dual-incretin to produce substantial weight loss
Authors: Seeley R.
Published: May 2024

We are in the midst of a revolution when it comes to treating individuals with obesity. "Incretin" and "Dual-Incretin" drugs now can produce weight loss that was only possible via bariatric surgery just five years ago. Key questions remain concerning just how these drugs exert these powerful effects and how those effects compare to weight loss induced by bariatric surgery. Evidence points toward these drugs not just being "anorexic" agents that reduce food intake but rather lowering the "set-point" for body weight/body fat. The presentation will focus on how weight is regulated and how that system interacts with these newest classes of drugs.

Citation Format: R. Seeley. Mechanisms for the effects of incretin and dual-incretin to produce substantial weight loss [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED03-02.
Abstract ED10-01: PI3K past, present, and future
Authors: Vasan N.
Published: May 2024

The PI3K pathway has long remained a fertile ground for drug discovery in cancer, including in estrogen receptor positive metastatic breast cancer. It has also remained a pathway difficult to drug effectively due to on target toxicities. New strategies to overcome these toxicities have manifested in novel drug types and management strategies for patients. Here I discuss the PI3K pathway in signaling and oncogenesis, current therapies inhibiting PI3K, mechanisms limiting efficacy, and increasing the PI3K therapeutic window with a focus on mutant selective PI3K inhibitors. Finally, I will expound on the translational future of the PI3K field, highlighting advances in biomarker discovery, tumor correlative analysis, and patient advocacy.

Citation Format: N. Vasan. PI3K past, present, and future [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED10-01.
Abstract PO1-02-01: T Cell Receptor Sequencing to Monitor Pelareorep-Induced Expansion of Tumor Infiltrating Lymphocytes
Authors: Trauger Richard , Loghmani Houra , Coffey Matt , Salvador Fernando , Gavilá Joaquín , Manso Luis , Pascual Tomás , Prat Aleix , Heineman Thomas
Published: May 2024

Background: Tumor infiltrating lymphocytes (TILs) represent a major immunological tumor control mechanism that is associated with better prognosis in breast cancer. We have previously reported the effect of pelareorep (pela), an intravenously delivered, non-engineered oncolytic reovirus, on a composite measurement of TILs and tumor cellularity (CelTIL) from the AWARE-1 window-of-opportunity study in patients with early breast cancer (eBC). These results showed treatment increased in CelTIL scores especially in the atezolizumab group. To confirm and extend these findings we applied T cell receptor sequencing of matched tumor tissue and whole blood pre and post-treatment from the AWARE-1 study to further explore the effects of pela therapy on TILs. Methods: Newly diagnosed HR+/HER2- eBC patients were enrolled into two cohorts: Cohort 1: pela + letrozole (n=10); and Cohort 2: pela + letrozole + atezolizumab (n=10). Pela was administered on days 1, 2 and 8, 9, and atezolizumab was given on day 3. Tumor biopsies (FFPE samples) collected pre-treatment (~D-23) and on day ~21 when tumors were surgically removed. T cell fraction analysis and T cell receptor sequencing were performed by Adaptive Biotechnology (Seattle, Washington) Immunoseq protocol. Results: As was shown for the CelTIL scores, an increase in the tumor T cell fraction, a direct measurement of TILs, was observed at 1-month post-treatment in both cohorts with a mean percent increase of 21% for Cohort 1 and 67% for Cohort 2. Through TCR-sequencing of tumor tissue, we identified TIL clones and tracked their differential abundance in tumor tissue and blood post-treatment. The results of this analysis at Day 21 showed a mean post-treatment expansion of 10 tumor specific clones in the blood for Cohort 1, and a mean post-treatment increase of 40 tumor specific clones for Cohort 2. Conclusions: These results confirm the previously reported CelTIL results from AWARE-1 on pela-induced increases in TILs and demonstrate the expansion of these clones in both tumor and blood as a consequence of pela therapy for HR+/HER2- breast cancer.

Citation Format: Richard Trauger, Houra Loghmani, Matt Coffey, Fernando Salvador, Joaquín Gavilá, Luis Manso, Tomás Pascual, Aleix Prat, Thomas Heineman. T Cell Receptor Sequencing to Monitor Pelareorep-Induced Expansion of Tumor Infiltrating Lymphocytes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-01.
Abstract PO1-04-07: Disitamab vedotin, a clinical stage HER2-directed antibody-drug conjugate, shows potent antitumor activity as a monotherapy and in combination with tucatinib in preclinical breast cancer models
Authors: Willis Kelsi , Hein Renee , Snead Katie , Thurman Robert , Kulukian Anita
Published: May 2024

Disitamab vedotin (DV, RC48-ADC) is an antibody-drug conjugate (ADC) that targets cancers expressing HER2. DV consists of an anti-HER2 monoclonal antibody, disitamab, conjugated with the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a cleavable vedotin linker. DV has multimodal antitumor mechanisms of action that include direct cytotoxicity of HER2-expressing cancer cells and bystander effect-based cytotoxicity of neighboring cells, both of which are mediated by the intracellular release of MMAE. Released MMAE can also induce immunogenic cell death, which promotes immune cell recruitment to the tumor. In addition, DV stimulates Fc-gamma receptor mediated antibody-dependent cellular cytotoxicity, which can lead to target cell death. DV also inhibits HER2-activated downstream signaling pathways, further blocking cell growth, survival, and proliferation. Previously, we showed the cytotoxic activity of DV against a panel of breast cancer cell lines with varying levels of HER2 expression, including the HER2-low range. Here, we sought to further characterize the preclinical antitumor activity of DV in patient-derived 3D models and patient-derived xenographs (PDX). In cultured breast cancer cells, DV was more potent and internalized to a greater magnitude than the HER2-directed ADCs trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). In patient-derived 3D models, DV had superior activity compared to T-DXd. We further explored whether dual HER2 targeting with DV in combination with the HER2-selective oral TKI tucatinib improved the antitumor outcomes. In PDX models with varying HER2 IHC levels and models refractory to T-DXd, DV as a monotherapy and in combination with tucatinib showed significant tumor growth inhibition. This result is consistent with previous in vitro results that showed increased cytotoxicity of the combination of DV and tucatinib in cell lines with a wide range of HER2 expression, which may be mechanistically attributed to elevated HER2 cell surface levels upon treatment with tucatinib. Overall, these findings provide scientific rationale to explore DV in HER2-positive and HER2-low breast cancer patients as a monotherapy or in combination with tucatinib.

Citation Format: Kelsi Willis, Renee Hein, Katie Snead, Robert Thurman, Anita Kulukian. Disitamab vedotin, a clinical stage HER2-directed antibody-drug conjugate, shows potent antitumor activity as a monotherapy and in combination with tucatinib in preclinical breast cancer models [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-07.