bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S1 from Transcriptional Phenocopies of Deleterious KEAP1 Mutations Correlate with Survival Outcomes in Lung Cancer Treated with Immunotherapy
Authors: Scalera Stefano , Ricciuti Biagio , Marinelli Daniele , Mazzotta Marco , Cipriani Laura , Bon Giulia , Schiavoni Giulia , Terrenato Irene , Di Federico Alessandro , Alessi Joao V. , Fanciulli Maurizio , Ciuffreda Ludovica , De Nicola Francesca , Goeman Frauke , Caravagna Giulio , Santini Daniele , De Maria Ruggero , Cappuzzo Federico , Ciliberto Gennaro , Jamal-Hanjani Mariam , Awad Mark M. , McGranahan Nicholas , Maugeri-Saccà Marcello
Published: October 2024

Supplementary Figure 1. Study workflow
Supplemental Tables S1-S7 from Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma
Authors: Kazandjian Dickran , Diamond Benjamin , Papadimitriou Marios , Hill Elizabeth , Sklavenitis-Pistofidis Romanos , Ziccheddu Bachisio , Blaney Patrick , Chojnacka Monika , Durante Michael , Maclachlan Kylee , Young Ryan , Usmani Saad , Davies Faith , Getz Gad , Ghobrial Irene , Korde Neha , Morgan Gareth , Maura Francesco , Landgren Ola
Published: October 2024

Supplemental Tables S1-S7
Supplemental Figure S8 from Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma
Authors: Kazandjian Dickran , Diamond Benjamin , Papadimitriou Marios , Hill Elizabeth , Sklavenitis-Pistofidis Romanos , Ziccheddu Bachisio , Blaney Patrick , Chojnacka Monika , Durante Michael , Maclachlan Kylee , Young Ryan , Usmani Saad , Davies Faith , Getz Gad , Ghobrial Irene , Korde Neha , Morgan Gareth , Maura Francesco , Landgren Ola
Published: October 2024

Supplemental Figure S8: EPRISM Outcomes using Significant KRD/R Genomic Lesions.
Supplemental Figure S6 from Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma
Authors: Kazandjian Dickran , Diamond Benjamin , Papadimitriou Marios , Hill Elizabeth , Sklavenitis-Pistofidis Romanos , Ziccheddu Bachisio , Blaney Patrick , Chojnacka Monika , Durante Michael , Maclachlan Kylee , Young Ryan , Usmani Saad , Davies Faith , Getz Gad , Ghobrial Irene , Korde Neha , Morgan Gareth , Maura Francesco , Landgren Ola
Published: October 2024

Supplemental Figure S6: Genomic Clustering of NDMM and HR-SMM.
Supplementary Figure S3 from Targeting the Dendritic Cell-Secreted Immunoregulatory Cytokine CCL22 Alleviates Radioresistance
Authors: Bugno Jason , Wang Liangliang , Yu Xianbin , Cao Xuezhi , Wang Jiaai , Huang Xiaona , Yang Kaiting , Piffko Andras , Chen Katherine , Luo Stephen Y. , Naccasha Emile , Hou Yuzhu , Fu Sherry , He Chuan , Fu Yang-xin , Liang Hua L. , Weichselbaum Ralph R.
Published: October 2024

Supplementary Figure S3. Changes in MC38 tumor cDC populations after local RT.
Supplementary Figure S3 from Spatial Transcriptome Mapping of the Desmoplastic Growth Pattern of Colorectal Liver Metastases by In Situ Sequencing Reveals a Biologically Relevant Zonation of the Desmoplastic Rim
Authors: Andersson Axel , Escriva Conde Maria , Surova Olga , Vermeulen Peter , Wählby Carolina , Nilsson Mats , Nyström Hanna
Published: October 2024

Supplementary Figure S3. Supplementary to Figure 3 in the main text. Average number of reads of the rim-enriched genes in the different clusters.
Supplementary Figure S2 from Spatial Transcriptome Mapping of the Desmoplastic Growth Pattern of Colorectal Liver Metastases by In Situ Sequencing Reveals a Biologically Relevant Zonation of the Desmoplastic Rim
Authors: Andersson Axel , Escriva Conde Maria , Surova Olga , Vermeulen Peter , Wählby Carolina , Nilsson Mats , Nyström Hanna
Published: October 2024

Supplementary Figure S2. Sample exclusion. Sample excluded from the study due to poor tissue quality.
Supplementary Figure S1 from Spatial Transcriptome Mapping of the Desmoplastic Growth Pattern of Colorectal Liver Metastases by In Situ Sequencing Reveals a Biologically Relevant Zonation of the Desmoplastic Rim
Authors: Andersson Axel , Escriva Conde Maria , Surova Olga , Vermeulen Peter , Wählby Carolina , Nilsson Mats , Nyström Hanna
Published: October 2024

Supplementary Figure S1. Gene distribution and bin radius analysis for sampled reads. Panel A shows the distribution of the number of genes (out of the 15 reads per bin) for each sample. Each bin contains eight unique genes on average. Panel B shows the radius of each bin, i.e., the distance between 15th nearest read and the bin center. The bin radius varied between 5 and 40 μm, with an average bin radius of 17 μm, corresponding to the approximate size of a cell.
Supplementary Figure S9 from Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis
Authors: Lizardo Michael M. , Hughes Christopher , Huang Yue Z. , Shyp Taras , Delaidelli Alberto , Zhang Hai-Feng , Shaool Sol Snir , Renner Annalena F. , Burwag Farez , Sayles Leanne C. , Lee Alex G. , Sweet-Cordero Alejandro , Sorensen Poul H.
Published: October 2024

Fig. S9. Distribution of NFE2L2 and MYC transcripts in light and heavy polysomal fractions and ectopic expression of NRF2.
Supplementary Figure S8 from Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis
Authors: Lizardo Michael M. , Hughes Christopher , Huang Yue Z. , Shyp Taras , Delaidelli Alberto , Zhang Hai-Feng , Shaool Sol Snir , Renner Annalena F. , Burwag Farez , Sayles Leanne C. , Lee Alex G. , Sweet-Cordero Alejandro , Sorensen Poul H.
Published: October 2024

Fig. S8. CR-1-31B effects on NRF2 protein stability
Supplementary Figure S13 from Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis
Authors: Lizardo Michael M. , Hughes Christopher , Huang Yue Z. , Shyp Taras , Delaidelli Alberto , Zhang Hai-Feng , Shaool Sol Snir , Renner Annalena F. , Burwag Farez , Sayles Leanne C. , Lee Alex G. , Sweet-Cordero Alejandro , Sorensen Poul H.
Published: October 2024

Fig. S13. eFT226 diminishes NRF2 expression and metastatic capacity in MNNG OS cells
Supplementary Table S8 from Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy–Induced Immune-Related Adverse Events in Melanoma
Authors: Monson Kelsey R. , Ferguson Robert , Handzlik Joanna E. , Xiong Jiahan , Dagayev Sasha , Morales Leah , Chat Vylyny , Bunis Anabelle , Sreenivasaiah Chaitra , Dolfi Sonia , Tenney Daniel J. , Shao Yongzhao , Osman Iman , Weber Jeffrey S. , Kirchhoff Tomas
Published: October 2024

Supplementary Table S8. Confusion matrix for top LASSO-regularized and cross-validated logistic regression model predicting severe (grade 3-4) irAEs (age, stage, and CD22, PAG1, CD33, HNRNPU, and FCGR2C gene expression) in COMBO-treated patients.
Supplementary Table S4 from Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy–Induced Immune-Related Adverse Events in Melanoma
Authors: Monson Kelsey R. , Ferguson Robert , Handzlik Joanna E. , Xiong Jiahan , Dagayev Sasha , Morales Leah , Chat Vylyny , Bunis Anabelle , Sreenivasaiah Chaitra , Dolfi Sonia , Tenney Daniel J. , Shao Yongzhao , Osman Iman , Weber Jeffrey S. , Kirchhoff Tomas
Published: October 2024

Supplementary Table S4: Predicted PPI for differentially expressed genes identified in the study.
Supplementary Table S1 from Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy–Induced Immune-Related Adverse Events in Melanoma
Authors: Monson Kelsey R. , Ferguson Robert , Handzlik Joanna E. , Xiong Jiahan , Dagayev Sasha , Morales Leah , Chat Vylyny , Bunis Anabelle , Sreenivasaiah Chaitra , Dolfi Sonia , Tenney Daniel J. , Shao Yongzhao , Osman Iman , Weber Jeffrey S. , Kirchhoff Tomas
Published: October 2024

Supplementary Table S1. irAE event and grades for the patient population.
Supplementary Figure S1 from Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models
Authors: Talbot Lindsay J. , Chabot Ashley , Ross Aaron B. , Beckett Alexandra , Nguyen Phuong , Fleming Andrew , Chockley Peter J. , Shepphard Heather , Wang Jian , Gottschalk Stephen , DeRenzo Christopher
Published: October 2024

ELISA evaluation of IL8 and CXCL16 in models
Supplementary Data S1 from Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models
Authors: Talbot Lindsay J. , Chabot Ashley , Ross Aaron B. , Beckett Alexandra , Nguyen Phuong , Fleming Andrew , Chockley Peter J. , Shepphard Heather , Wang Jian , Gottschalk Stephen , DeRenzo Christopher
Published: October 2024

Raw RNAseq data for chemokine ligand screen
Supplementary Figure S6 from Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy–Induced Immune-Related Adverse Events in Melanoma
Authors: Monson Kelsey R. , Ferguson Robert , Handzlik Joanna E. , Xiong Jiahan , Dagayev Sasha , Morales Leah , Chat Vylyny , Bunis Anabelle , Sreenivasaiah Chaitra , Dolfi Sonia , Tenney Daniel J. , Shao Yongzhao , Osman Iman , Weber Jeffrey S. , Kirchhoff Tomas
Published: October 2024

Supplementary Figure S6. Correlation plots for predictor variables in cross-validation logistic regression models.
Supplementary Table 7 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay
Authors: Nakamura Yoshiaki , Tsukada Yuichiro , Matsuhashi Nobuhisa , Murano Tatsuro , Shiozawa Manabu , Takahashi Yusuke , Oki Eiji , Goto Masahiro , Kagawa Yoshinori , Kanazawa Akiyoshi , Ohta Takashi , Ouchi Akira , Bando Hideaki , Uchigata Hiroshi , Notake Chiemi , Ikematsu Hiroaki , Yoshino Takayuki
Published: October 2024

Supplementary Table 7. Risk of recurrence based on ctDNA detection early on adjuvant chemotherapy in patients with stage II or higher CRC, Tables to accompany Supplementary Figure 9A-B.
Supplementary Table S1 from Update on Recommendations for Surveillance for Children with Predisposition to Hematopoietic Malignancy
Authors: Maese Luke D. , Wlodarski Marcin W. , Kim Sun Young , Bertuch Alison A. , Bougeard Gaelle , Chang Vivian Y. , Godley Lucy A. , Khincha Payal P. , Kuiper Roland P. , Lesmana Harry , McGee Rose B. , McReynolds Lisa J. , Meade Julia , Plon Sharon E. , Savage Sharon A. , Scollon Sarah R. , Scott Hamish S. , Walsh Michael F. , Nichols Kim E. , Porter Christopher C.
Published: October 2024

Consensus classification of hereditary hematologic malignancies
Supplementary Table S8 from The Innate Immune Landscape of dMMR/MSI Cancers Predicts the Outcome of Nivolumab Treatment: Results from the Drug Rediscovery Protocol
Authors: Zeverijn Laurien J. , Geurts Birgit S. , Battaglia Thomas W. , van Berge Henegouwen Jade M. , de Wit Gijs F. , Hoes Louisa R. , van der Wijngaart Hanneke , van der Noort Vincent , Roepman Paul , de Leng Wendy W.J. , Jansen Anne M.L. , Chalabi Myriam , van Herpen Carla M.L. , Devriese Lot A. , Erdkamp Frans L.G. , Labots Mariette , de Jonge Maja J.A. , Kerver Emile D. , Bins Adriaan D. , Leek Lindsay V.M. , Notohardjo Jessica C.L. , van den Eertwegh Alfonsus J.M. , Wessels Lodewyk F.A. , Verheul Henk M.W. , Gelderblom Hans , van de Haar Joris , Voest Emile E.
Published: October 2024

Supplementary Table S8. Overview per patient included in biomarker analysis.
Supplementary Table S5 from The Innate Immune Landscape of dMMR/MSI Cancers Predicts the Outcome of Nivolumab Treatment: Results from the Drug Rediscovery Protocol
Authors: Zeverijn Laurien J. , Geurts Birgit S. , Battaglia Thomas W. , van Berge Henegouwen Jade M. , de Wit Gijs F. , Hoes Louisa R. , van der Wijngaart Hanneke , van der Noort Vincent , Roepman Paul , de Leng Wendy W.J. , Jansen Anne M.L. , Chalabi Myriam , van Herpen Carla M.L. , Devriese Lot A. , Erdkamp Frans L.G. , Labots Mariette , de Jonge Maja J.A. , Kerver Emile D. , Bins Adriaan D. , Leek Lindsay V.M. , Notohardjo Jessica C.L. , van den Eertwegh Alfonsus J.M. , Wessels Lodewyk F.A. , Verheul Henk M.W. , Gelderblom Hans , van de Haar Joris , Voest Emile E.
Published: October 2024

Supplementary Table S5. Baseline characteristics and clinical outcome data of melanoma cohort.
Supplementary Table S4 from FDA Approval Summary: Asciminib for Ph+ CML in Chronic Phase Treated with Two or More Tyrosine Kinase Inhibitors and for the T315I Mutation
Authors: Pamuk Gulsum E. , Chow Edwin C.Y. , Ionan Alexei C. , Chen Haiyan , Lee Shwu-Luan , Hsu Vicky , Grimstein Manuela , Zheng Nan , Sun Jielin , Charlab Rosane , Gehrke Brenda J. , Vallejo Jonathon , Ehrlich Lori A. , de Claro R. Angelo , Theoret Marc R.
Published: October 2024

The list of preferred terms included in grouped terms used for safety analysis in X2101 trial
Supplementary Figure S3 from Clinical Value of Liquid Biopsy in Patients with FGFR2 Fusion–Positive Cholangiocarcinoma During Targeted Therapy
Authors: González-Medina Alberto , Vila-Casadesús Maria , Gomez-Rey Marina , Fabregat-Franco Carles , Sierra Alexandre , Tian Tian V. , Castet Florian , Castillo Gloria , Matito Judit , Martinez Paola , Miquel Josep M. , Nuciforo Paolo , Pérez-López Raquel , Macarulla Teresa , Vivancos Ana
Published: October 2024

Supplementary Figure S3. FGFR2 intron 17 genome browser view.
Figure 1 from Elacestrant in ER+, HER2− Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups
Authors: Bardia Aditya , Cortés Javier , Bidard François-Clément , Neven Patrick , Garcia-Sáenz José , Aftimos Phillipe , O’Shaughnessy Joyce , Lu Janice , Tonini Giulia , Scartoni Simona , Paoli Alessandro , Binaschi Monica , Wasserman Tomer , Kaklamani Virginia
Published: October 2024

PFS in patients who received prior ET+CDK4/6i ≥12 months in the metastatic setting. Kaplan–Meier estimates of PFS in patients with ESR1-mutated tumors and prior ET+CDK4/6i ≥12 months in the metastatic setting (n = 159).
Data from Early Detection of Malignant and Premalignant Peripheral Nerve Tumors Using Cell-Free DNA Fragmentomics
Authors: Sundby R. Taylor , Szymanski Jeffrey J. , Pan Alexander C. , Jones Paul A. , Mahmood Sana Z. , Reid Olivia H. , Srihari Divya , Armstrong Amy E. , Chamberlain Stacey , Burgic Sanita , Weekley Kara , Murray Béga , Patel Sneh , Qaium Faridi , Lucas Andrea N. , Fagan Margaret , Dufek Anne , Meyer Christian F. , Collins Natalie B. , Pratilas Christine A. , Dombi Eva , Gross Andrea M. , Kim AeRang , Chrisinger John S.A. , Dehner Carina A. , Widemann Brigitte C. , Hirbe Angela C. , Chaudhuri Aadel A. , Shern Jack F.
Published: October 2024

AbstractPurpose:
Early detection of neurofibromatosis type 1 (NF1)–associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.
Experimental Design:
cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures.
Results:
The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration–based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management.
Conclusions:
Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.
Data from Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy–Induced Immune-Related Adverse Events in Melanoma
Authors: Monson Kelsey R. , Ferguson Robert , Handzlik Joanna E. , Xiong Jiahan , Dagayev Sasha , Morales Leah , Chat Vylyny , Bunis Anabelle , Sreenivasaiah Chaitra , Dolfi Sonia , Tenney Daniel J. , Shao Yongzhao , Osman Iman , Weber Jeffrey S. , Kirchhoff Tomas
Published: October 2024

AbstractPurpose:
Immune checkpoint inhibition (ICI) shows benefits in adjuvant (AT) and neoadjuvant melanoma treatments. However, ICI frequently induces severe immune-related adverse events (irAE). Unlike metastatic disease, in which irAEs are a clinical trade-off for treatment that improves survival, the toxicity burden from ICI in the AT setting is a substantial clinical problem urging for irAE-predictive biomarkers.
Experimental Design:
We assessed postsurgical, pre–ICI treatment peripheral CD4+ and CD8+ T cells from clinical trial patients (CheckMate 915) treated with AT nivolumab (n = 130) or ipilimumab/nivolumab (COMBO, n = 82). Performing RNA sequencing differential gene expression analysis, we tested baseline differences associated with severe (grades 3–5) irAEs and constructed an irAE-predictive model using least absolute shrinkage and selection operator–regularized logistic regression.
Results:
The analysis of predicted protein–protein interactions among differentially expressed genes in peripheral CD4+ cells revealed significant enrichment of the spleen tyrosine kinase (SYK) pathway, associated with severe irAEs in COMBO-treated patients. This gene expression signature predicted severe-irAE COMBO patients (χ2P value = 0.001) with 73% accuracy and was independent of disease recurrence (P = 0.79). The irAE-predictive model incorporating this gene expression signature demonstrated 82% accuracy (χ2P value = 8.91E−06).
Conclusions:
We identified baseline gene expression differences in key immune pathways of peripheral blood T cells from COMBO-treated patients with grades 3 to 5 irAEs and defined a SYK-related gene signature correctly identifying ∼60% of COMBO-treated patients with grades 3 to 5 irAEs. This finding aligns with our previous work linking anti-CTLA4 irAEs with a germline variant associated with high SYK expression. This gene signature may serve as a baseline biomarker of severe grade 3 to 5 irAE risk, which is especially important in AT treatment.
Data from Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models
Authors: Talbot Lindsay J. , Chabot Ashley , Ross Aaron B. , Beckett Alexandra , Nguyen Phuong , Fleming Andrew , Chockley Peter J. , Shepphard Heather , Wang Jian , Gottschalk Stephen , DeRenzo Christopher
Published: October 2024

AbstractPurpose:
Clinical efficacy of chimeric antigen receptor (CAR) T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We sought to determine the primary chemokines secreted by OS and evaluate the efficacy of B7-H3.CAR T cells expressing the cognate receptors.
Experimental Design:
We developed a pipeline to identify chemokines secreted by OS by correlating RNA-seq data with chemokine protein detected in media from fresh surgical specimens. We identified CXCR2 and CXCR6 as promising receptors for enhancing CAR T-cell homing against OS. We evaluated the homing kinetics and efficiency of CXCR2- and CXCR6.T cells and homing, cytokine production, and antitumor activity of CXCR2- and CXCR6.B7-H3.CAR T cells in vitro and in vivo.
Results:
T cells transgenically expressing CXCR2 or CXCR6 exhibited ligand-specific enhanced migration over T cells modified with nonfunctional control receptors. Differential homing kinetics were observed, with CXCR2.T-cell homing quickly and plateauing early, whereas CXCR6.T cells took longer to home but achieved a similar plateau. When expressed in B7-H3.CAR T cells, CXCR2- and CXCR6 modification conferred enhanced homing toward OS in vitro and in vivo. CXCR2- and CXCR6-B7-H3.CAR-treated mice experienced prolonged survival in a metastatic model compared with B7-H3.CAR T-cell-treated mice.
Conclusions:
Our patient-based pipeline identified targets for chemokine receptor modification of CAR T cells targeting OS. CXCR2 and CXCR6 expression enhanced the homing and anti-OS activity of B7-H3.CAR T cells. These findings support clinical evaluation of CXCR-modified CAR T cells to improve adoptive cell therapy for patients with OS.
Data from Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia
Authors: Marrero Richard J. , Wu Huiyun , Cao Xueyuan , Parcha Phani Krishna , Elsayed Abdelrahman H. , Inaba Hiroto , Kuo Dennis John , Degar Barbara A. , Heym Kenneth , Taub Jeffrey W. , Lacayo Norman , Pui Ching-Hon , Ribeiro Raul C. , Rubnitz Jeffrey E. , Pounds Stanley B. , Lamba Jatinder K.
Published: October 2024

AbstractPurpose:
Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML.
Experimental Design:
ACS10 score groups (low, ≤0, or high, >0) were evaluated for association with event-free survival (EFS) and overall survival (OS) by three randomized treatment arms in patients treated on the AML02 (NCT00136084) and AML08 (NCT00703820) clinical trials: AML02 low-dose ara-C (LDAC arm, n = 91), AML02 + AML08 high-dose ara-C (HDAC arm, n = 194), and AML08 clofarabine + ara-C (Clo/ara-C arm, n = 105) induction I regimens.
Results:
Within the low-ACS10 score (≤0) group, significantly improved EFS and OS were observed among patients treated with Clo/ara-C as compared with LDAC (EFS, HR = 0.45; 95% CI, 0.23–0.88; P = 0.020; OS, HR = 0.44; 95% CI, 0.19–0.99; P = 0.048). In contrast, within the high-ACS10 score group (score >0), augmentation with Clo/ara-C was not favorable as compared with LDAC (Clo/ara-C vs. LDAC, EFS, HR = 1.95; 95% CI, 1.05–3.63; P = 0.035; OS, HR = 2.10; 95% CI, 0.96–4.59; P = 0.063). Personalization models predicted 9% improvement in the outcome in ACS10 score–based tailored induction (Clo/ara-C for low and LDAC for high-ACS10 score groups) as compared with nonpersonalized approaches (P < 0.002).
Conclusions:
Our findings suggest that tailoring induction regimens using ACS10 scores can significantly improve outcomes in patients with AML. Given the SNPs are germline, preemptive genotyping can accelerate matching the most effective remission induction regimen.
Data from Update on Recommendations for Surveillance for Children with Predisposition to Hematopoietic Malignancy
Authors: Maese Luke D. , Wlodarski Marcin W. , Kim Sun Young , Bertuch Alison A. , Bougeard Gaelle , Chang Vivian Y. , Godley Lucy A. , Khincha Payal P. , Kuiper Roland P. , Lesmana Harry , McGee Rose B. , McReynolds Lisa J. , Meade Julia , Plon Sharon E. , Savage Sharon A. , Scollon Sarah R. , Scott Hamish S. , Walsh Michael F. , Nichols Kim E. , Porter Christopher C.
Published: October 2024

Abstract
Children harboring certain germline gene variants have an increased risk of developing myelodysplastic syndrome (MDS) and other hematopoietic malignancies (HM), such as leukemias and lymphomas. Recent studies have identified an expanding number of these predisposition genes, with variants most prevalent in children with MDS but also found in children with other HM. For some hematopoietic malignancy predispositions (HMP), specifically those with a high risk of MDS, early intervention through hematopoietic stem cell transplantation can favorably impact overall survival, providing a rationale for rigorous surveillance. A multidisciplinary panel of experts at the 2023 AACR Childhood Cancer Predisposition Workshop reviewed the latest advances in the field and updated prior 2017 surveillance recommendations for children with HMP. In addition to general guidance for all children with HMP, which includes annual physical examination, education about the signs and symptoms of HM, consultation with experienced providers, and early assessment by a hematopoietic stem cell transplantation specialist, the panel provided specific recommendations for individuals with a higher risk of MDS based on the affected gene. These recommendations include periodic and comprehensive surveillance for individuals with those syndromes associated with higher risk of MDS, including serial bone marrow examinations to monitor for morphologic changes and deep sequencing for somatic changes in genes associated with HM progression. This approach enables close monitoring of disease evolution based on the individual’s genetic profile. As more HMP-related genes are discovered and the disorders’ natural histories are better defined, these personalized recommendations will serve as a foundation for future guidelines in managing these conditions.
Supplementary Table 1 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Word document for Supplementary Table 1
Supplementary Table 1 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

PDF file for Supp Table 1
Supplementary Figure S15 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Supplementary Figure S15
Supplementary Figure S12 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Supplementary Figure S12
Supplementary Figure S11 from Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M.
Published: October 2024

Supplementary Figure S11
Figure S3 from Characterization of AB598, a CD39 Enzymatic Inhibitory Antibody for the Treatment of Solid Tumors
Authors: Anderson Amy E. , Parashar Kaustubh , Jin Ke , Clor Julie , Stagnaro Carlo E. , Vani Urvi , Singh Jaskirat , Chen Ada , Guan Yihong , Talukdar Priyanka , Sathishkumar Pavithra , Juat Damie J. , Singh Hema , Kushwaha Ritu , Zhao Xiaoning , Kaplan Angelo , Seitz Lisa , Walters Matthew J. , Fernandez-Salas Ester , Walker Nigel P.C. , Bowman Christine E.
Published: October 2024

Figure S3
Figure S2 from Characterization of AB598, a CD39 Enzymatic Inhibitory Antibody for the Treatment of Solid Tumors
Authors: Anderson Amy E. , Parashar Kaustubh , Jin Ke , Clor Julie , Stagnaro Carlo E. , Vani Urvi , Singh Jaskirat , Chen Ada , Guan Yihong , Talukdar Priyanka , Sathishkumar Pavithra , Juat Damie J. , Singh Hema , Kushwaha Ritu , Zhao Xiaoning , Kaplan Angelo , Seitz Lisa , Walters Matthew J. , Fernandez-Salas Ester , Walker Nigel P.C. , Bowman Christine E.
Published: October 2024

Figure S2
Table S4 from PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J.
Published: October 2024

Hallmark pathways enriched in NeoPalAna patients
Supplementary Data from FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models
Authors: Guo Qingsong , Gao Bei , Song Ruiwen , Li Weinan , Zhu Shulei , Xie Qian , Lou Sensen , Wang Lei , Shen Jiafei , Zhao Teng , Zhang Yifan , Wu Jinsong , Lu Wei , Yang Tong
Published: October 2024

Supplementary Data
Figure S3 from FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models
Authors: Guo Qingsong , Gao Bei , Song Ruiwen , Li Weinan , Zhu Shulei , Xie Qian , Lou Sensen , Wang Lei , Shen Jiafei , Zhao Teng , Zhang Yifan , Wu Jinsong , Lu Wei , Yang Tong
Published: October 2024

Supplementary Fig.S3
Figure S2 from FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models
Authors: Guo Qingsong , Gao Bei , Song Ruiwen , Li Weinan , Zhu Shulei , Xie Qian , Lou Sensen , Wang Lei , Shen Jiafei , Zhao Teng , Zhang Yifan , Wu Jinsong , Lu Wei , Yang Tong
Published: October 2024

Supplementary Fig.S2
Figure S3 from PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J.
Published: October 2024

Effect of RB1 knockdown on E2-induced gene expression
Figure S19 from PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J.
Published: October 2024

Additional BCM-7441 in vivo experiment data
Figure S1 from PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer
Authors: Chen Anran , Kim Beom-Jun , Mitra Aparna , Vollert Craig T. , Lei Jonathan T. , Fandino Diana , Anurag Meenakshi , Holt Matthew V. , Gou Xuxu , Pilcher Jacob B. , Goetz Matthew P. , Northfelt Donald W. , Hilsenbeck Susan G. , Marshall C. Gary , Hyer Marc L. , Papp Robert , Yin Shou-Yun , De Angelis Carmine , Schiff Rachel , Fuqua Suzanne A.W. , Ma Cynthia X. , Foulds Charles E. , Ellis Matthew J.
Published: October 2024

WEE1 mRNA and protein levels in ER+ breast cancer PDXs
Supplementary Tables 1-9 from The Vedotin Antibody–Drug Conjugate Payload Drives Platform-Based Nonclinical Safety and Pharmacokinetic Profiles
Authors: Neff-LaFord Haley D. , Carratt Sarah A. , Carosino Christopher , Everds Nancy , Cardinal Kristen A. , Duniho Steven , Schutten Melissa M. , Frantz Christopher , Zuch de Zafra Christina , Harstad Eric B.
Published: October 2024

Supplementary Tables 1-9
Supplementary Figure S4 from Blocking M2-Like Macrophage Polarization Using Decoy Oligodeoxynucleotide-Based Gene Therapy Prevents Immune Evasion for Pancreatic Cancer Treatment
Authors: Chen Chang-Jung , Wang Hao-Chen , Hou Ya-Chin , Wu Yi-Ying , Shieh Chi-Chang , Shan Yan-Shen
Published: October 2024

Supplementary Figure S4. H2O2 cannot independently activate JAK/STAT6 phosphorylation. The effect of H2O2 (100 nM) on JAK1, JAK3, STAT6, and CYBB total protein and phosphorylated protein expression was analyzed with Western blotting at indicated time points. GAPDH was used as a loading control. The bar graph depicts the ratio of CYBB/GAPDH. ns, not significant, compared to 0 h. Data represent the mean of 3 independent experiments.
Figure S4 from AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer
Authors: Nouri Mannan , Varkaris Andreas , Ridinger Maya , Dalrymple Susan L. , Dennehy Christopher M. , Isaacs John T. , Einstein David J. , Brennen W.N. , Balk Steven P.
Published: October 2024

Validation of drug screen hits in 2-D and 3-D.
Supplementary Table S1 from Discovery of Monovalent Direct Degraders of BRD4 that Act via the Recruitment of DCAF11
Authors: Parker Gregory S. , Toth Julia I. , Fish Sarah , Blanco Gabrielle , Kampert Taylor , Li Xiaoming , Yang Linette , Stumpf Craig R. , Steadman Kenneth , Jamborcic Aleksandar , Chien Stephen , Daniele Elizabeth , Dearie Alejandro , Leriche Geoffray , Bailey Simon , Thompson Peggy A.
Published: October 2024

Supplementary Table S1 shows CRISPR screen hits
Supplementary Table S2 from The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading
Authors: Sudhakar Niranjan , Yan Larry , Qiryaqos Fadia , Engstrom Lars D. , Laguer Jade , Calinisan Andrew , Hebbert Allan , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Ketcham John M. , Ivetac Anthony , Smith Christopher R. , Lawson J. David , Rahbaek Lisa , Clarine Jeffrey , Nguyen Natalie , Saechao Barbara , Parker Cody , Elliott Adam J. , Vanderpool Darin , He Leo , Hover Laura D. , Fernandez-Banet Julio , Coma Silvia , Pachter Jonathan A. , Hallin Jill , Marx Matthew A. , Briere David M. , Christensen James G. , Olson Peter , Haling Jacob , Khare Shilpi
Published: October 2024

Supplementary Table S2 shows the antitumor activity of MRTX0902 and adagrasib in a panel of human KRAS G12C-mutant tumor cell line-derived and patient-derived xenograft models.
Data from Characterization of AB598, a CD39 Enzymatic Inhibitory Antibody for the Treatment of Solid Tumors
Authors: Anderson Amy E. , Parashar Kaustubh , Jin Ke , Clor Julie , Stagnaro Carlo E. , Vani Urvi , Singh Jaskirat , Chen Ada , Guan Yihong , Talukdar Priyanka , Sathishkumar Pavithra , Juat Damie J. , Singh Hema , Kushwaha Ritu , Zhao Xiaoning , Kaplan Angelo , Seitz Lisa , Walters Matthew J. , Fernandez-Salas Ester , Walker Nigel P.C. , Bowman Christine E.
Published: October 2024

Abstract
AB598 is a CD39 inhibitory antibody being pursued for the treatment of solid tumors in combination with chemotherapy and immunotherapy. CD39 metabolizes extracellular adenosine triphosphate (eATP), an alarmin capable of promoting antitumor immune responses, into adenosine, an immuno-inhibitory metabolite. By inhibiting CD39, the consumption of eATP is reduced, resulting in a proinflammatory milieu in which eATP can activate myeloid cells to promote antitumor immunity. The preclinical characterization of AB598 provides a mechanistic rationale for combining AB598 with chemotherapy in the clinic. Chemotherapy can induce ATP release from tumor cells and, when preserved by AB598, both chemotherapy-induced eATP and exogenously added ATP promote the function of monocyte-derived dendritic cells via P2Y11 signaling. Inhibition of CD39 in the presence of ATP can promote inflammasome activation in in vitro-derived macrophages, an effect mediated by P2X7. In a MOLP8 murine xenograft model, AB598 results in full inhibition of intratumoral CD39 enzymatic activity, an increase in intratumoral ATP, a decrease of extracellular CD39 on tumor cells, and ultimately, control of tumor growth. In cynomolgus monkeys, systemic dosing of AB598 results in effective enzymatic inhibition in tissues, full peripheral and tissue target engagement, and a reduction in cell surface CD39 both in tissues and in the periphery. Taken together, these data support a promising therapeutic strategy of harnessing the eATP generated by standard-of-care chemotherapies to prime the tumor microenvironment for a productive antitumor immune response.
Data from The Vedotin Antibody–Drug Conjugate Payload Drives Platform-Based Nonclinical Safety and Pharmacokinetic Profiles
Authors: Neff-LaFord Haley D. , Carratt Sarah A. , Carosino Christopher , Everds Nancy , Cardinal Kristen A. , Duniho Steven , Schutten Melissa M. , Frantz Christopher , Zuch de Zafra Christina , Harstad Eric B.
Published: October 2024

Abstract
Nonclinical safety and pharmacokinetic data for monomethyl auristatin E (MMAE) and 14 vedotin antibody–drug conjugates (ADC) were evaluated to determine patterns of toxicity, consistency of pharmacokinetic results, and species differences between rats and monkeys. Most nonclinical toxicities were antigen-independent, common across ADCs, and included hematologic, lymphoid, and reproductive toxicity related to MMAE pharmacology. Hematologic toxicity was the dose-limiting toxicity (DLT) or predominant toxicity for the majority of vedotin ADCs in both species. Tissue expression of the targeted antigen of an ADC rarely correlated with DLT; only two ADCs had antigen-dependent skin DLTs. For two additional ADCs, antigen-dependent delivery of MMAE in the bone marrow may have exacerbated the antigen-independent hematologic DLT. The highest tolerated doses and pharmacokinetics were similar within a given species, with rats tolerating higher doses than monkeys. Studies longer than 1 month in duration detected the same or fewer toxicities than 1-month studies and had no additional findings that affected the human risk assessment. These data support opportunities to streamline ADC toxicity assessments without compromising human starting dose selection or target organ identification.
Data from Targeting Chemoresistance in Advanced Bladder Cancers with a Novel Adjuvant Strategy
Authors: Seremak Juliette R. , Gupta Kunj Bihari , Bonigala Sunilkanth , Liu Elise , Marshall Brendan , Zhi Wenbo , Bokhtia Riham M. , Panda Siva S. , Lokeshwar Vinata B. , Lokeshwar Bal L.
Published: October 2024

Abstract
Advanced urinary bladder cancer is characterized by rapid progression and development of therapy resistance. About 30% of the patients are diagnosed with high-grade tumors (grade > T2a). A typical nonsurgical treatment is systemic chemotherapy using cisplatin (C) and gemcitabine (G). However, treatment failure and subsequent disease progression are common in treated patients, and adjuvant therapies are not significantly effective. The therapeutic potential of a molecular hybrid of ursolic acid (UA), a pentacyclic-triterpene conjugated to N-methyl piperazine (UA4), was tested on both naïve (WT) and gemcitabine-resistant (GemR) variants of two human invasive bladder cancer cell lines, 5637 and T24. UA4 killed 5637 (4 µmol/L), T24 (4 µmol/L) WT, and GemR cells in vitro at equal potency. Pretreatment with UA4 followed by G synergistically killed WT and GemR cells by >50% compared with G followed by UA4. Oral gavage of UA4 (100 mg/kg) inhibited WT and GemR tumor growth in athymic mice. UA4 + G was more effective against GemR tumors than either drug alone. Studies revealed cytotoxic autophagy as a mechanism of UA4 cytotoxicity. UA4 induced moderate apoptosis in T24 but not in 5637 cells. Mitochondrial integrity and function were most affected by UA4 because of high levels of reactive oxygen species, disruption of mitochondrial membrane, and cell cycle arrest. These effects were enhanced in the UA4 + G combination. UA4 was well-tolerated in mice, and oral gavage led to a serum level >1 µmol/L with no systemic toxicity. These results show the potential of UA4 as a nontoxic alternative treatment for high-grade bladder cancer.
Data from Blocking M2-Like Macrophage Polarization Using Decoy Oligodeoxynucleotide-Based Gene Therapy Prevents Immune Evasion for Pancreatic Cancer Treatment
Authors: Chen Chang-Jung , Wang Hao-Chen , Hou Ya-Chin , Wu Yi-Ying , Shieh Chi-Chang , Shan Yan-Shen
Published: October 2024

Abstract
M2-like macrophages exhibit immunosuppressive activity and promote pancreatic cancer progression. Reactive oxygen species (ROS) affect macrophage polarization; however, the mechanism remains unclear. This study aimed to elucidate the underlying molecular basis and design a gene therapy to inhibit M2-like polarization. Microarray analysis and immunofluorescence staining were performed in M1-like and M2-like macrophages to ascertain the expression of CYBB, a major intracellular ROS source. Coculture assay and syngeneic orthotopic pancreatic cancer mice models were used to study the mechanism of M2-like skewing. Decoy oligodeoxynucleotides (ODNs) were designed to manipulate CYBB transcription to inhibit M2-like polarization and control tumor growth. Lipopolysaccharide treatment polarized U937 cells to M1-like macrophages in which CYBB expression was increased. In contrast, coculture with PANC-1 cells induced M2-like polarization in U937 cells with CYBB downregulation. High CD204 M2-like expression in combination with low CYBB expression was associated with the worst prognosis in patients with pancreatic cancer. STAT6 and HDAC2 in U937 cells were activated by cancer cell–derived IL4 after coculture and then bound to the CYBB promoter to repress CYBB expression, resulting in M2-like polarization. Diphenyleneiodonium, 8λ³-iodatricyclo[7.4.0.02,⁷]trideca-1(13),2,4,6,9,11-hexaen-8-ylium chloride that inhibits ROS production could block this action. Knockdown of STAT6 and HDAC2 also inhibited M2-like polarization and maintained the M1-like phenotype of U937 cells after coculture. Decoy ODNs interrupting the binding of STAT6 to the CYBB promoter counteracted M2-like polarization and tumor growth and triggered antitumor immunity in vivo. Gene therapy using STAT6-CYBB decoy ODNs can inhibit M2-like polarization, representing a potential therapeutic tool for pancreatic cancer.
Data from AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer
Authors: Nouri Mannan , Varkaris Andreas , Ridinger Maya , Dalrymple Susan L. , Dennehy Christopher M. , Isaacs John T. , Einstein David J. , Brennen W.N. , Balk Steven P.
Published: October 2024

Abstract
Polo-like kinase 1 (PLK1) inhibitors have had limited antitumor efficacy as single agents, and focus of current efforts is on combination therapies. We initially confirmed that the PLK1-specific inhibitor onvansertib (ONV) could enhance responses to a PARP inhibitor (olaparib) in prostate cancer xenografts. To identify more effective combinations, we screened a library of bioactive compounds for efficacy in combination with ONV in LNCaP prostate cancer cells, which identified a series of compounds including multiple AKT inhibitors. We confirmed in vitro synergy between ONV and the AKT inhibitor ipatasertib (IPA) and found that the combination increased apoptosis. Mechanistic studies showed that ONV increased expression of the antiapoptotic protein SURVIVIN and that this was mitigated by IPA. Studies in three PTEN-deficient prostate cancer xenograft models showed that cotreatment with IPA and ONV led to significant tumor growth inhibition compared with monotherapies. Together, these in vitro and in vivo studies demonstrate that the efficacy of PLK1 antagonists can be enhanced by PARP or AKT inhibition and support further development of these combination therapies.
Supplementary Figure S1 from Cancer History and Social Support Impact Colorectal Cancer Screening Utilization by Race/Ethnicity
Authors: Tsai Meng-Han , Lee Minjee , Coughlin Steven S. , Eberth Jan M. , Rogers Charles R.
Published: October 2024

In Supplementary Figure S1, seven exclusion criteria were applied based on the study purpose. As a result, 73,869 eligible participants were included for full analyses.
Supplementary Figure S1 from Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia
Authors: Strickland Lincoln N. , Liu Wendao , Hussein Usama , Mardik Nicolette , Chen Xian , Mills Tingting , Vornik Lana A. , Savage Michelle I. , Sei Shizuko , Clifford John , Eltzschig Holger K. , Brown Powel H. , Zhao Zhongming , McAllister Florencia , Bailey-Lundberg Jennifer M.
Published: October 2024

Supplementary Figure S1. Description of IHC quantification methods.
Data from Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia
Authors: Strickland Lincoln N. , Liu Wendao , Hussein Usama , Mardik Nicolette , Chen Xian , Mills Tingting , Vornik Lana A. , Savage Michelle I. , Sei Shizuko , Clifford John , Eltzschig Holger K. , Brown Powel H. , Zhao Zhongming , McAllister Florencia , Bailey-Lundberg Jennifer M.
Published: October 2024

Abstract
Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression. AB-680, or vehicle control, was administered using oral gavage delivery 3 days/week at 10 mg/kg, beginning when the mice were 2 months old and lasting 3 months. We euthanized the mice at 5 months old. In the KC model, we quantified significantly less pancreatitis, early and advanced PanIN, and quantified a significant increase in M1 macrophages in AB-680-treated mice. Single-cell RNA sequencing (scRNA-seq) of pancreata of AB-680-treated mice revealed increased infiltration of CD4+ T cells, CD8+ T cells, and mature B cells. The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment.

Prevention Relevance: Previous studies found PanIN lesions in healthy pancreata. Not all progress to PDAC, suggesting a window for enhanced antitumor immunity through immunoprevention therapy. CD73 inhibition in our study prevents PanIN progression, reduces immune-suppressive macrophages and expands TCR and BCR unique clonotypes, highlighting an encouraging therapeutic avenue for high-risk individuals.