bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Mutant KRAS mediates circARFGEF2 biogenesis to promote lymphatic metastasis of pancreatic ductal adenocarcinoma
Authors: Kong Yao , Luo Yuming , Zheng Shangyou , Yang Jiabin , Zhang Dingwen , Zhao Yue , Zheng Hanhao , An Mingjie , Lin Yan , Ai Le , Diao Xiarao , Lin Qing , Chen Changhao , Chen Rufu
Published: September 2023

Abstract
Circular RNAs (circRNAs) contribute to cancer stemness, proliferation, and metastasis. The biogenesis of circRNAs can be impacted by the genetic landscape of tumors. Herein, we identified a novel circRNA, circARFGEF2 (hsa_circ_0060665), which was upregulated in KRASG12D pancreatic ductal adenocarcinoma (PDAC) and positively associated with KRASG12D PDAC lymph node (LN) metastasis. CircARFGEF2 overexpression significantly facilitated KRASG12D PDAC LN metastasis in vitro and in vivo. Mechanistically, circARFGEF2 biogenesis in KRASG12D PDAC was significantly activated by the alternative splicing factor QKI-5, which recruited U2AF35 to facilitate spliceosome assembly. QKI-5 bound the QKI binding motifs and neighboring reverse complement sequence in intron 3 and 6 of ARFGEF2 pre-mRNA to facilitate circARFGEF2 biogenesis. CircARFGEF2 sponged miR-1205 and promoted the activation of JAK2, which phosphorylated STAT3 to trigger KRASG12D PDAC lymphangiogenesis and LN metastasis. Importantly, circARFGEF2 silencing significantly inhibited LN metastasis in the KrasG12D/+Trp53R172H/+Pdx-1-Cre (KPC) mouse PDAC model. These findings provide insight into the mechanism and metastasis-promoting function of mutant KRAS-mediated circRNA biogenesis.
Supplementary Table S3 from A Phase Ib Trial of AVID200, a TGFβ 1/3 Trap, in Patients with Myelofibrosis
Authors: Mascarenhas John , Migliaccio Anna Rita , Kosiorek Heidi , Bhave Rupali , Palmer Jeanne , Kuykendall Andrew , Mesa Ruben , Rampal Raajit K. , Gerds Aaron T. , Yacoub Abdulraheem , Pettit Kristen , Talpaz Moshe , Komrokji Rami , Kremyanskaya Marina , Gonzalez Agapito , Fabris Frank , Johnson Kathryn , Dougherty Mikaela , McGovern Erin , Arango Ossa Juan , Domenico Dylan , Farnoud Noushin , Weinberg Rona Singer , Kong Amy , Najfeld Vesna , Vannucchi Alessandro Maria , Arciprete Francesca , Zingariello Maria , Falchi Mario , Salama Mohamed E. , Mead-Harvey Carolyn , Dueck Amylou , Varricchio Lilian , Hoffman Ronald
Published: September 2023

Representativeness of Study Participants.
Supplementary Table S1 from A Phase Ib Trial of AVID200, a TGFβ 1/3 Trap, in Patients with Myelofibrosis
Authors: Mascarenhas John , Migliaccio Anna Rita , Kosiorek Heidi , Bhave Rupali , Palmer Jeanne , Kuykendall Andrew , Mesa Ruben , Rampal Raajit K. , Gerds Aaron T. , Yacoub Abdulraheem , Pettit Kristen , Talpaz Moshe , Komrokji Rami , Kremyanskaya Marina , Gonzalez Agapito , Fabris Frank , Johnson Kathryn , Dougherty Mikaela , McGovern Erin , Arango Ossa Juan , Domenico Dylan , Farnoud Noushin , Weinberg Rona Singer , Kong Amy , Najfeld Vesna , Vannucchi Alessandro Maria , Arciprete Francesca , Zingariello Maria , Falchi Mario , Salama Mohamed E. , Mead-Harvey Carolyn , Dueck Amylou , Varricchio Lilian , Hoffman Ronald
Published: September 2023

Clinical info on the platelets-responsive and non-responsive patients
Supplementary Figure S7 from A Phase Ib Trial of AVID200, a TGFβ 1/3 Trap, in Patients with Myelofibrosis
Authors: Mascarenhas John , Migliaccio Anna Rita , Kosiorek Heidi , Bhave Rupali , Palmer Jeanne , Kuykendall Andrew , Mesa Ruben , Rampal Raajit K. , Gerds Aaron T. , Yacoub Abdulraheem , Pettit Kristen , Talpaz Moshe , Komrokji Rami , Kremyanskaya Marina , Gonzalez Agapito , Fabris Frank , Johnson Kathryn , Dougherty Mikaela , McGovern Erin , Arango Ossa Juan , Domenico Dylan , Farnoud Noushin , Weinberg Rona Singer , Kong Amy , Najfeld Vesna , Vannucchi Alessandro Maria , Arciprete Francesca , Zingariello Maria , Falchi Mario , Salama Mohamed E. , Mead-Harvey Carolyn , Dueck Amylou , Varricchio Lilian , Hoffman Ronald
Published: September 2023

Effects of AVID200 therapy on plasma TGFβ levels.
Supplementary Table S3 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: September 2023

Correlation of 89Zr PET Uptake and HER2 Status
Supplementary Figure S8 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: September 2023

PIK3CD S367L demonstrate increased phosphorylation of AKT. Upon progression, 1 patient developed a PIK3CD S367L mutation (location indicated in gene map), a variant of undetermined significance in the carboxy terminal C2 domain. Above, western blot demonstrating pAKT expression in 3T3 cells stably expressing p110δ WT or mutations at p110d E1021K, L806M, S367L, R894Q, G971E, or R338W relative to non-transformed parental 3T3 cells, which do not express p110δ. Below, lollipop plot of PIK3CD.
Supplementary Figure S5 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: September 2023

Lesions without pre-treatment ERBB2 amplification appear less likely to respond to pembrolizumab and trastuzumab induction. Lesion-level CT response after 1 dose of pembrolizumab and trastuzumab among patients with baseline tumor-matched ctDNA color-coded according to pre-treatment a, ctDNA ERBB2 amplification status and b, tissue WES ERBB2 amplification status.
Table S4 from A Novel HOXA10-Associated 5-Gene–Based Prognostic Signature for Stratification of Short-term Survivors of Pancreatic Ductal Adenocarcinoma
Authors: Kisling Sophia G. , Atri Pranita , Shah Ashu , Cox Jesse L. , Sharma Sunandini , Smith Lynette M. , Ghersi Dario , Batra Surinder K.
Published: September 2023

PDAC cohort validated genes
Table S3 from A Novel HOXA10-Associated 5-Gene–Based Prognostic Signature for Stratification of Short-term Survivors of Pancreatic Ductal Adenocarcinoma
Authors: Kisling Sophia G. , Atri Pranita , Shah Ashu , Cox Jesse L. , Sharma Sunandini , Smith Lynette M. , Ghersi Dario , Batra Surinder K.
Published: September 2023

Enriched genes in STS
Table S2 from A Novel HOXA10-Associated 5-Gene–Based Prognostic Signature for Stratification of Short-term Survivors of Pancreatic Ductal Adenocarcinoma
Authors: Kisling Sophia G. , Atri Pranita , Shah Ashu , Cox Jesse L. , Sharma Sunandini , Smith Lynette M. , Ghersi Dario , Batra Surinder K.
Published: September 2023

HOXA10-driven gene set
Supplementary Data 1 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: September 2023

Taqman probes used for quantitative PCR.
Figure S1 from A Novel HOXA10-Associated 5-Gene–Based Prognostic Signature for Stratification of Short-term Survivors of Pancreatic Ductal Adenocarcinoma
Authors: Kisling Sophia G. , Atri Pranita , Shah Ashu , Cox Jesse L. , Sharma Sunandini , Smith Lynette M. , Ghersi Dario , Batra Surinder K.
Published: September 2023

Validation of HOXA10-specific antibody
Suppl. Figure 2 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: September 2023

ENG knockdown leads to downregulation of pro-angiogenic and pro-metastatic gene signatures in MPNST cells.
Suppl. Figure 1 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: September 2023

Analysis of ENG expression and plasma circulating sEVs in human PNSTs.
Supplementary Table S1 from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer
Authors: Traphagen Nicole A. , Schwartz Gary N. , Tau Steven , Roberts Alyssa M. , Jiang Amanda , Hosford Sarah R. , Marotti Jonathan D. , Goen Abigail E. , Romo Bianca A. , Johnson Anneka L. , Duffy Emily-Claire K. , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon M. , Kolling Fred , Miller Todd W.
Published: September 2023

Table S1. Results of genome-wide CRISPR/Cas9 screening of HCC-1428/LTED cells.
Supplementary Data 1 from Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated Macrophages
Authors: Yuan Wei , Zhang Qian , Gu Danling , Lu Chenfei , Dixit Deobrat , Gimple Ryan C. , Gao Yisu , Gao Jiancheng , Li Daqi , Shan Danyang , Hu Lang , Li Lu , Li Yangqing , Ci Shusheng , You Hao , Yan Linping , Chen Kexin , Zhao Ningwei , Xu Chuanhai , Lan Jianyun , Liu Dong , Zhang Junxia , Shi Zhumei , Wu Qiulian , Yang Kailin , Zhao Linjie , Qiu Zhixin , Lv Deguang , Gao Wei , Yang Hui , Lin Fan , Wang Qianghu , Man Jianghong , Li Chaojun , Tao Weiwei , Agnihotri Sameer , Qian Xu , Mack Stephen C. , Zhang Nu , You Yongping , Rich Jeremy N. , Sun Guan , Wang Xiuxing
Published: September 2023

Supplementary Figure S1-S7, and Supplementary table S1
Supplementary Figure S9 from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer
Authors: Traphagen Nicole A. , Schwartz Gary N. , Tau Steven , Roberts Alyssa M. , Jiang Amanda , Hosford Sarah R. , Marotti Jonathan D. , Goen Abigail E. , Romo Bianca A. , Johnson Anneka L. , Duffy Emily-Claire K. , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon M. , Kolling Fred , Miller Todd W.
Published: September 2023

Characterization of PDX model CTG-3346
Supplementary Figure S4 from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer
Authors: Traphagen Nicole A. , Schwartz Gary N. , Tau Steven , Roberts Alyssa M. , Jiang Amanda , Hosford Sarah R. , Marotti Jonathan D. , Goen Abigail E. , Romo Bianca A. , Johnson Anneka L. , Duffy Emily-Claire K. , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon M. , Kolling Fred , Miller Todd W.
Published: September 2023

Supplementary Figure S4- ER overexpression converts E2 from a growth promoter to a growth suppressor.
Supplementary Figure S12 from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer
Authors: Traphagen Nicole A. , Schwartz Gary N. , Tau Steven , Roberts Alyssa M. , Jiang Amanda , Hosford Sarah R. , Marotti Jonathan D. , Goen Abigail E. , Romo Bianca A. , Johnson Anneka L. , Duffy Emily-Claire K. , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon M. , Kolling Fred , Miller Todd W.
Published: September 2023

Supplementary Figure S12- ER overexpression promotes E2-induced R-loop formation.
Supplementary Figure S11 from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer
Authors: Traphagen Nicole A. , Schwartz Gary N. , Tau Steven , Roberts Alyssa M. , Jiang Amanda , Hosford Sarah R. , Marotti Jonathan D. , Goen Abigail E. , Romo Bianca A. , Johnson Anneka L. , Duffy Emily-Claire K. , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon M. , Kolling Fred , Miller Todd W.
Published: September 2023

Supplementary Figure S11- E2 stimulation induces DNA replication stress.
Supplementary Table S1 from Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial
Authors: Abel Melissa L. , Takahashi Nobuyuki , Peer Cody , Redon Christophe E. , Nichols Samantha , Vilimas Rasa , Lee Min-Jung , Lee Sunmin , Shelat Meenakshi , Kattappuram Robbie , Sciuto Linda , Pinkiert Danielle , Graham Chante , Butcher Donna , Karim Baktiar , Sharma Ajit Kumar , Malin Justin , Kumar Rajesh , Schultz Christopher W. , Goyal Shubhank , del Rivero Jaydira , Krishnamurthy Manan , Upadhyay Deep , Schroeder Brett , Sissung Tristan , Tyagi Manoj , Kim Jung , Pommier Yves , Aladjem Mirit , Raffeld Mark , Figg William Douglas , Trepel Jane , Xi Liqiang , Desai Parth , Thomas Anish
Published: September 2023

Whole exome sequencing results
Supplementary Table S8 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Table S8. Corpus uterine cancer patient characteristics, median survival, and Multivariate Cox Regression Modeling
Supplementary Table S4 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Table S4. RNAscope Antibodies and Probes
Supplementary Table S2 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Table S2. Pancreatic cancer patient characteristics by lorazepam prescription records
Supplementary Table S13 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Table S13. Colon cancer patient characteristics, median survival, and Multivariate Cox Regression Modeling.
Supplementary Table S12 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Table S12. Ovarian cancer patient characteristics, median survival, and Multivariate Cox Regression Modeling.
Supplementary Table S10 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Table S10. Invasive nevi and melanoma patient characteristics, median survival, and Multivariate Cox Regression Modeling
Supplementary Figure S6 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Figure S6. LOR is associated with worse progression-free survival across multiple cancer types.
Supplementary Figure S5 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Figure S5. LOR treatment increases STAT3 phosphorylation
Supplementary Table S4 from Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)
Authors: Tovey Holly , Sipos Orsolya , Parker Joel S. , Hoadley Katherine A. , Quist Jelmar , Kernaghan Sarah , Kilburn Lucy , Salgado Roberto , Loi Sherene , Kennedy Richard D. , Roxanis Ioannis , Gazinska Patrycja , Pinder Sarah E. , Bliss Judith , Perou Charles M. , Haider Syed , Grigoriadis Anita , Tutt Andrew , Cheang Maggie Chon U.
Published: September 2023

Supplementary Table 4 - Representativeness of Study Participants
Supplementary Figure S4 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Figure S4. KPC subcutaneous syngeneic allograft tumors are acidic and express GPR68.
Supplementary Table S3 from Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)
Authors: Tovey Holly , Sipos Orsolya , Parker Joel S. , Hoadley Katherine A. , Quist Jelmar , Kernaghan Sarah , Kilburn Lucy , Salgado Roberto , Loi Sherene , Kennedy Richard D. , Roxanis Ioannis , Gazinska Patrycja , Pinder Sarah E. , Bliss Judith , Perou Charles M. , Haider Syed , Grigoriadis Anita , Tutt Andrew , Cheang Maggie Chon U.
Published: September 2023

Supplemetary table 3 - Change in signature scores from primary to recurrence
Supplementary Table S2 from Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)
Authors: Tovey Holly , Sipos Orsolya , Parker Joel S. , Hoadley Katherine A. , Quist Jelmar , Kernaghan Sarah , Kilburn Lucy , Salgado Roberto , Loi Sherene , Kennedy Richard D. , Roxanis Ioannis , Gazinska Patrycja , Pinder Sarah E. , Bliss Judith , Perou Charles M. , Haider Syed , Grigoriadis Anita , Tutt Andrew , Cheang Maggie Chon U.
Published: September 2023

Supplementary table 2 - Model estimates for logistic regression models of objective response rate and linear regression models of restricted PFS by treatment group
Supplementary Figure S5 from Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)
Authors: Tovey Holly , Sipos Orsolya , Parker Joel S. , Hoadley Katherine A. , Quist Jelmar , Kernaghan Sarah , Kilburn Lucy , Salgado Roberto , Loi Sherene , Kennedy Richard D. , Roxanis Ioannis , Gazinska Patrycja , Pinder Sarah E. , Bliss Judith , Perou Charles M. , Haider Syed , Grigoriadis Anita , Tutt Andrew , Cheang Maggie Chon U.
Published: September 2023

Heatmap showing clustering of all module scores filtered for a significant interaction with treatment. Our original clusters are shown against the new clusters at the top of the heatmap.
Supplementary Figure S4 from Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)
Authors: Tovey Holly , Sipos Orsolya , Parker Joel S. , Hoadley Katherine A. , Quist Jelmar , Kernaghan Sarah , Kilburn Lucy , Salgado Roberto , Loi Sherene , Kennedy Richard D. , Roxanis Ioannis , Gazinska Patrycja , Pinder Sarah E. , Bliss Judith , Perou Charles M. , Haider Syed , Grigoriadis Anita , Tutt Andrew , Cheang Maggie Chon U.
Published: September 2023

This is an example of DDR-deficient case with high TILs and low gene-expression measurements. These cases were confirmed to have high TIL content (black delineation) and are characterized by both high tumour area- stromal area ratio as well as a high tumour cell- stromal cell ratio. Moreover, all these cases were characterized by high grade features, such as necrosis (blue delineation), high mitotic activity (green arrow), and high levels of atypia (blue arrow), and all had a solid growth pattern, with no formation of glands.
Supplementary Figure S1 from Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Seshadri Mukund , Parker Mark D. , Cortes Gomez Eduardo , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E.
Published: September 2023

Supplementary Figure S1. BZD prescriptions are associated with improved disease-specific pancreatic cancer patient survival
Supplementary Figure S2 from Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)
Authors: Tovey Holly , Sipos Orsolya , Parker Joel S. , Hoadley Katherine A. , Quist Jelmar , Kernaghan Sarah , Kilburn Lucy , Salgado Roberto , Loi Sherene , Kennedy Richard D. , Roxanis Ioannis , Gazinska Patrycja , Pinder Sarah E. , Bliss Judith , Perou Charles M. , Haider Syed , Grigoriadis Anita , Tutt Andrew , Cheang Maggie Chon U.
Published: September 2023

Changes in A. CIN70, B. RPS and C. PARPi7 from treatment naïve primary tumours to post-treatment metastatic samples in an independent dataset.
Multiple metastatic samples are included for some patients.
𝛃 coefficients and p-values presented for timepoint term from linear regression models with a random effect for patient to account for multiple samples from patients.
Supplemental Figure 1 from Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: September 2023

Selection of the transcriptomic signatures for the unsupervised clustering
Supplementary Table S4 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: September 2023

Supplementary Table S4: Targeted Lesions at Baseline. The baseline sum of targeted lesions (mm) for each patient, determined at baseline by CT for RECIST1.1 evaluation.
Supplementary Figure S7 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: September 2023

Supplementary Figure 7: Copy-number profile of CCNE1 in cfDNA
Supplementary Figure S5 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: September 2023

Supplementary Figure 5: Sensitivity of variant calling methods on cfDNA
Supplementary Figure S2 from A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: September 2023

Supplementary Figure S2. DXd immunohistochemistry in a patient treated with 6.4 mg/kg DS-6157a (A) pre-treatment and (B) on treatment (Cycle 2, Day 10)
Supplementary Figure S4 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: September 2023

Supplementary Figure 4: Distribution of cfDNA fragment length
Supplementary Materials 1 from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: September 2023

Supplementary Materials. Study Protocol
Supplementary Figure S5 from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: September 2023

Supplementary Figure S5. Kaplan–Meier estimates of time to progression and overall survival according to etiology in the per-protocol population. (A) Time to progression. (B) Overall survival. (C) Progression-free survival.
Supplementary Figure S3 from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: September 2023

Supplementary Figure S3. Kaplan–Meier estimates of time to progression and overall survival according to BCLC stage in the per-protocol population. (A) Time to progression. (B) Overall survival. (C) Progression-free survival.
Supplementary Table S6 from CD49d Expression Identifies a Biologically Distinct Subtype of Chronic Lymphocytic Leukemia with Inferior Progression-Free Survival on BTK Inhibitor Therapy
Authors: Alsadhan Anfal , Chen Jonathan , Gaglione Erika M. , Underbayev Chingiz , Tuma Pamela L. , Tian Xin , Freeman Lita A. , Baskar Sivasubramanian , Nierman Pia , Soto Susan , Itsara Andy , Ahn Inhye E. , Sun Clare , Bibikova Elena , Hartmann Tanja Nicole , Mhibik Maissa , Wiestner Adrian
Published: September 2023

Supplementary Table S6. DEGs for Baseline Comparison of CD49d+ and CD49d
Supplementary Figure S6 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

Subasumstat induces interferon-response genes in a dose responsive fashion
Supplementary Table S3 from CD49d Expression Identifies a Biologically Distinct Subtype of Chronic Lymphocytic Leukemia with Inferior Progression-Free Survival on BTK Inhibitor Therapy
Authors: Alsadhan Anfal , Chen Jonathan , Gaglione Erika M. , Underbayev Chingiz , Tuma Pamela L. , Tian Xin , Freeman Lita A. , Baskar Sivasubramanian , Nierman Pia , Soto Susan , Itsara Andy , Ahn Inhye E. , Sun Clare , Bibikova Elena , Hartmann Tanja Nicole , Mhibik Maissa , Wiestner Adrian
Published: September 2023

Supplementary Table S3: Representativeness of Study Participants
Supplementary Figure S3 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

Subasumstatinduces IFNβ in immune cells.
Supplementary Figure S2 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

Expression of IFNB1 and ISG15 as a function of subasumstat exposure.
Supplementary Figure S19 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

Subasumstat initiates cell death and cytotoxic T cell activity
Supplementary Figure S18 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

Correlation of MKI67 gene expression levels to Percent MIL113 Positivity for Tumors 7 and 8
Supplementary Figure S17 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

Subasumstat-induced Interferon signature expression level is predicted by the CD8/CD68 ratio of the baseline tumor
Supplementary Figure S5 from Evaluation of Somatic Mutations in Urine Samples as a Noninvasive Method for the Detection and Molecular Classification of Endometrial Cancer
Authors: Costas Laura , Onieva Irene , Pelegrina Beatriz , Marin Fátima , Carmona Álvaro , López-Querol Marta , Frias-Gomez Jon , Peremiquel-Trillas Paula , Martínez José Manuel , Dorca Eduard , Brunet Joan , Pineda Marta , Ponce Jordi , Matias-Guiu Xavier , de Sanjosé Silvia , Bosch Francesc Xavier , Alemany Laia , Paytubi Sonia
Published: September 2023

This graph illustrates the relationship between the number of interrogated genes and the sensitivity and specificity values.
Supplementary Figure 1 from Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors
Authors: Vieito Maria , Moreno Victor , Spreafico Anna , Brana Irene , Wang Judy S. , Preis Meir , Hernández Tatiana , Genta Sofia , Hansen Aaron R. , Doger Bernard , Galvao Vladimir , Lenox Laurie , Brown Regina J. , Kalota Anna , Mehta Jaydeep , Pastore Friederike , Patel Bharvin , Mistry Pankaj , Gu Junchen , Lauring Josh , Patel Manish R.
Published: September 2023

Supplementary Figure 1: Overall Response Over Time on JNJ-64619178 Treatment A. Dose Cohorts 0.5 mg - 1.5 mg (schedule A&B). B. Dose Cohorts 2.0 mg - 4.0 mg (schedule A&B)
Supplementary Table S1 from Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non–Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042)
Authors: Gadgeel Shirish M. , Miao Jieling , Riess Jonathan W. , Moon James , Mack Philip C. , Gerstner Gregory J. , Burns Timothy F. , Taj Asma , Akerley Wallace L. , Dragnev Konstantin H. , Laudi Noel , Redman Mary W. , Gray Jhanelle E. , Gandara David R. , Kelly Karen
Published: September 2023

Supplementary Table 1. Dose Modifications for Docetaxel and Trametinib
Supplementary Figure S1 from Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non–Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042)
Authors: Gadgeel Shirish M. , Miao Jieling , Riess Jonathan W. , Moon James , Mack Philip C. , Gerstner Gregory J. , Burns Timothy F. , Taj Asma , Akerley Wallace L. , Dragnev Konstantin H. , Laudi Noel , Redman Mary W. , Gray Jhanelle E. , Gandara David R. , Kelly Karen
Published: September 2023

Supplementary Figure 1. Progression-Free Survival and Overall Survival in patients with cancers with TP53 co-mutations, and STK11 co-mutations.
Data from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

AbstractPurpose:
Cancer drug development is currently limited by a paradigm of preclinical evaluation that does not adequately recapitulate the complexity of the intact human tumor microenvironment (TME). To overcome this, we combined trackable intratumor microdosing (CIVO) with spatial biology readouts to directly assess drug effects in patient tumors in situ.
Experimental design:
In a first-of-its-kind phase 0 clinical trial, we explored the effects of an investigational stage SUMOylation-activating enzyme (SAE) inhibitor, subasumstat (TAK-981) in 12 patients with head and neck carcinoma (HNC). Patients scheduled for tumor resection received percutaneous intratumor injections of subasumstat and vehicle control 1 to 4 days before surgery, resulting in spatially localized and graded regions of drug exposure (∼1,000–2,000 μm in diameter). Drug-exposed (n = 214) and unexposed regions (n = 140) were compared by GeoMx Digital Spatial Profiler, with evaluation at single-cell resolution in a subset of these by CosMx Spatial Molecular Imager.
Results:
Localized regions of subasumstat exposure revealed SUMO pathway inhibition, elevation of type I IFN response, and inhibition of cell cycle across all tumor samples. Single-cell analysis by CosMx demonstrated cell-cycle inhibition specific to the tumor epithelium, and IFN pathway induction commensurate with a TME shift from immune-suppressive to immune-permissive.
Conclusions:
Pairing CIVO with spatial profiling enabled detailed investigation of response to subasumstat across a diverse sampling of native and intact TME. We demonstrate that drug mechanism of action can be directly evaluated in a spatially precise manner in the most translationally relevant setting: an in situ human tumor.
Data from A Phase Ib Trial of AVID200, a TGFβ 1/3 Trap, in Patients with Myelofibrosis
Authors: Mascarenhas John , Migliaccio Anna Rita , Kosiorek Heidi , Bhave Rupali , Palmer Jeanne , Kuykendall Andrew , Mesa Ruben , Rampal Raajit K. , Gerds Aaron T. , Yacoub Abdulraheem , Pettit Kristen , Talpaz Moshe , Komrokji Rami , Kremyanskaya Marina , Gonzalez Agapito , Fabris Frank , Johnson Kathryn , Dougherty Mikaela , McGovern Erin , Arango Ossa Juan , Domenico Dylan , Farnoud Noushin , Weinberg Rona Singer , Kong Amy , Najfeld Vesna , Vannucchi Alessandro Maria , Arciprete Francesca , Zingariello Maria , Falchi Mario , Salama Mohamed E. , Mead-Harvey Carolyn , Dueck Amylou , Varricchio Lilian , Hoffman Ronald
Published: September 2023

AbstractPurpose:
Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by systemic symptoms, cytopenias, organomegaly, and bone marrow fibrosis. JAK2 inhibitors afford symptom and spleen burden reduction but do not alter the disease course and frequently lead to thrombocytopenia. TGFβ, a pleiotropic cytokine elaborated by the MF clone, negatively regulates normal hematopoiesis, downregulates antitumor immunity, and promotes bone marrow fibrosis. Our group previously showed that AVID200, a potent and selective TGFβ 1/3 trap, reduced TGFβ1-induced proliferation of human mesenchymal stromal cells, phosphorylation of SMAD2, and collagen expression. Moreover, treatment of MF mononuclear cells with AVID200 led to increased numbers of progenitor cells (PC) with wild-type JAK2 rather than JAK2V617F.
Patients and Methods:
We conducted an investigator-initiated, multicenter, phase Ib trial of AVID200 monotherapy in 21 patients with advanced MF.
Results:
No dose-limiting toxicity was identified at the three dose levels tested, and grade 3/4 anemia and thrombocytopenia occurred in 28.6% and 19.0% of treated patients, respectively. After six cycles of therapy, two patients attained a clinical benefit by IWG-MRT criteria. Spleen and symptom benefits were observed across treatment cycles. Unlike other MF-directed therapies, increases in platelet counts were noted in 81% of treated patients with three patients achieving normalization. Treatment with AVID200 resulted in potent suppression of plasma TGFβ1 levels and pSMAD2 in MF cells.
Conclusions:
AVID200 is a well-tolerated, rational, therapeutic agent for the treatment of patients with MF and should be evaluated further in patients with thrombocytopenic MF in combination with agents that target aberrant MF intracellular signaling pathways.
Data from A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: September 2023

AbstractPurpose:
To evaluate DS-6157a, an antibody–drug conjugate targeting G protein–coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST).
Patients and Methods:
In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy.
Results:
A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed.
Conclusions:
Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.
Data from Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction
Authors: Salari Keyan , Sundi Debasish , Lee Jason J. , Wu Shulin , Wu Chin-Lee , DiFiore Gabrielle , Yan Q. Robert , Pienkny Andrew , Lee Chi K. , Oberlin Daniel , Barme Greg , Piser Joel , Kahn Robert , Collins Edward , Phillips Kevin G. , Caruso Vincent M. , Goudarzi Mahdi , Garcia-Ransom Monica , Lentz Peter S. , Evans-Holm Martha E. , MacBride Andrew R. , Fischer Daniel S. , Haddadzadeh Iden J. , Mazzarella Brian C. , Gray Joe W. , Koppie Theresa M. , Bicocca Vincent T. , Levin Trevor G. , Lotan Yair , Feldman Adam S.
Published: September 2023

AbstractPurpose:
Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk.
Experimental Design:
This is a multicenter case–control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology.
Results:
uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%.
Conclusions:
uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.