bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figures 1-7 from Creating MHC-Restricted Neoantigens with Covalent Inhibitors That Can Be Targeted by Immune Therapy
Authors: Hattori Takamitsu , Maso Lorenzo , Araki Kiyomi Y. , Koide Akiko , Hayman James , Akkapeddi Padma , Bang Injin , Neel Benjamin G. , Koide Shohei
Published: April 2023

Supplementary Figure S1 shows size exclusion chromatography profiles of products of the refolding reactions for p/MHCs utilized in this study.
Supplementary Figure S2 shows binding properties of antibodies to sotorasib-KRAS(G12C) peptide conjugates in complex with MHCs over the course of the affinity maturation campaign.
Supplementary Figure S3 shows binding profiles of a deep mutational scanning library before and after sorting.
Supplementary Figure S4 shows HLA expression of cell lines.
Supplementary Figure S5 shows cytotoxic effects of the R023 scDb on sotorasib-treated tumor cells.
Supplementary Figure S6 shows binding analysis of “pan-HLA” antibody phage clones to p/MHC complexes.
Supplementary Figure S7 shows binding analysis of antibody phage clones to an ibrutinib-BTK peptide conjugate in complex with MHC.
Supplementary Video 2 from Bone Metastasis Initiation Is Coupled with Bone Remodeling through Osteogenic Differentiation of NG2+ Cells
Authors: Zhang Weijie , Xu Zhan , Hao Xiaoxin , He Tiancheng , Li Jiasong , Shen Yichao , Liu Kai , Gao Yang , Liu Jun , Edwards David G. , Muscarella Aaron M. , Wu Ling , Yu Liqun , Xu Longyong , Chen Xi , Wu Yi-Hsuan , Bado Igor L. , Ding Yunfeng , Aguirre Sergio , Wang Hai , Gugala Zbigniew , Satcher Robert L. , Wong Stephen T.C. , Zhang Xiang H.-F.
Published: April 2023

Supplemantary Video 2, LLC1 cells under monoculture
Table S3 from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma
Authors: Chow Ryan D. , Michaels Tai , Bellone Stefania , Hartwich Tobias M.P. , Bonazzoli Elena , Iwasaki Akiko , Song Eric , Santin Alessandro D.
Published: April 2023

Supplementary Table S3: Predicted pathogenic/deleterious variants by exome sequencing.
Table S2 from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma
Authors: Chow Ryan D. , Michaels Tai , Bellone Stefania , Hartwich Tobias M.P. , Bonazzoli Elena , Iwasaki Akiko , Song Eric , Santin Alessandro D.
Published: April 2023

Supplementary Table S2: HLA genotype calls.
Supplementary Raw Data from Bone Metastasis Initiation Is Coupled with Bone Remodeling through Osteogenic Differentiation of NG2+ Cells
Authors: Zhang Weijie , Xu Zhan , Hao Xiaoxin , He Tiancheng , Li Jiasong , Shen Yichao , Liu Kai , Gao Yang , Liu Jun , Edwards David G. , Muscarella Aaron M. , Wu Ling , Yu Liqun , Xu Longyong , Chen Xi , Wu Yi-Hsuan , Bado Igor L. , Ding Yunfeng , Aguirre Sergio , Wang Hai , Gugala Zbigniew , Satcher Robert L. , Wong Stephen T.C. , Zhang Xiang H.-F.
Published: April 2023

summarized excel file containing the quantitative raw data and processed values in the manuscript
Supplementary Figures from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma
Authors: Chow Ryan D. , Michaels Tai , Bellone Stefania , Hartwich Tobias M.P. , Bonazzoli Elena , Iwasaki Akiko , Song Eric , Santin Alessandro D.
Published: April 2023

Supplementary Figure S1: Additional characterization of the clinical trial cohort.Supplementary Figure S2: Additional characterization of exome profiles and defining MLH1 methylation status.Supplementary Figure S3: JAK1 alterations are most frequent in endometrial cancer.Supplementary Figure S4: Final cell counts in each scRNA-seq sample.Supplementary Figure S5: Longitudinal transcriptional profiling of circulating immune cells before and after PD-1 blockade.Supplementary Figure S6: Differential abundance of cell neighborhoods after PD-1 immunotherapy.Supplementary Figure S7: Differential abundance of cell neighborhoods in JAK1-mutant tumors.Supplementary Figure S8: Transcriptional profiles of T and NK cells in responders vs non-responders.Supplementary Figure S9: Gene expression changes in T and NK cells following PD-1 immunotherapy.Supplementary Figure S10: Additional transcriptional characterization of CD16+ NK cells in epiR patients.
Supplementary Video 1A from Cell Competition Shapes Metastatic Latency and Relapse
Authors: Kim Kangsan , Huang Huocong , Parida Pravat Kumar , He Lan , Marquez-Palencia Mauricio , Reese Tanner C. , Kapur Payal , Brugarolas James , Brekken Rolf A. , Malladi Srinivas
Published: April 2023

Video shows displacement of Lat-M cells in cell competition. Lat-M cells (Green) surrounded by PA (Red) cells being displaced under
cell competition assay conditions.
Supplementary Figure from The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma
Authors: Hao Dapeng , Han Guangchun , Sinjab Ansam , Gomez-Bolanos Lorena Isabel , Lazcano Rossana , Serrano Alejandra , Hernandez Sharia D. , Dai Enyu , Cao Xuanye , Hu Jian , Dang Minghao , Wang Ruiping , Chu Yanshuo , Song Xingzhi , Zhang Jianhua , Parra Edwin R. , Wargo Jennifer A. , Swisher Stephen G. , Cascone Tina , Sepesi Boris , Futreal Andrew P. , Li Mingyao , Dubinett Steven M. , Fujimoto Junya , Solis Soto Luisa M. , Wistuba Ignacio I. , Stevenson Christopher S. , Spira Avrum , Shalapour Shabnam , Kadara Humam , Wang Linghua
Published: April 2023

Supplementary Figure from The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma
Supplementary Figure from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
Authors: Kohno Takashi , Kato Mamoru , Kohsaka Shinji , Sudo Tomohisa , Tamai Ikuo , Shiraishi Yuichi , Okuma Yusuke , Ogasawara Daisuke , Suzuki Tatsuya , Yoshida Teruhiko , Mano Hiroyuki
Published: April 2023

Supplementary Figure from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
Supplementary Data from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
Authors: Kohno Takashi , Kato Mamoru , Kohsaka Shinji , Sudo Tomohisa , Tamai Ikuo , Shiraishi Yuichi , Okuma Yusuke , Ogasawara Daisuke , Suzuki Tatsuya , Yoshida Teruhiko , Mano Hiroyuki
Published: April 2023

Supplementary Data from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
Supplementary Figure S8 from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Cholesterol overload activates AP-1 via ERK signaling to mediate invasion upon GRAMD1B loss in melanoma.
Supplementary Figure S6 from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Loss of GRAMD1B promotes tumor cell invasion in
human melanoma cells
Supplementary Figure S5 from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Supp. Fig. S5 shows that GRAMD1B is a metastasis suppressor
in human melanoma
Supplementary Figure S3 from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Validation of gramd1b depletion in zebrafish cells and tumors.
Supp Table S7 from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Supp Table S7: GSEA Analysis
Supp Table S6 from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Supp Table S6 Differentially Expressed Genes
Supp Table S1 from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Supplementary Table S1. List of genes predictive of metastasis from AVAST-M trial. 
Supplementary Data from Serial Profiling of Circulating Tumor DNA Identifies Dynamic Evolution of Clinically Actionable Genomic Alterations in High-Risk Neuroblastoma
Authors: Bosse Kristopher R. , Giudice Anna Maria , Lane Maria V. , McIntyre Brendan , Schürch Patrick M. , Pascual-Pasto Guillem , Buongervino Samantha N. , Suresh Sriyaa , Fitzsimmons Alana , Hyman Adam , Gemino-Borromeo Maria , Saggio Jennifer , Berko Esther R. , Daniels Alexander A. , Stundon Jennifer , Friedrichsen Megan , Liu Xin , Margolis Matthew L. , Li Marilyn M. , Tierno Marni Brisson , Oxnard Geoffrey R. , Maris John M. , Mossé Yael P.
Published: April 2023

Supplementary Data from Serial Profiling of Circulating Tumor DNA Identifies Dynamic Evolution of Clinically Actionable Genomic Alterations in High-Risk Neuroblastoma
Supplementary Figure from Proteogenomic Markers of Chemotherapy Resistance and Response in Triple-Negative Breast Cancer
Authors: Anurag Meenakshi , Jaehnig Eric J. , Krug Karsten , Lei Jonathan T. , Bergstrom Erik J. , Kim Beom-Jun , Vashist Tanmayi D. , Huynh Anh Minh Tran , Dou Yongchao , Gou Xuxu , Huang Chen , Shi Zhiao , Wen Bo , Korchina Viktoriya , Gibbs Richard A. , Muzny Donna M. , Doddapaneni Harshavardhan , Dobrolecki Lacey E. , Rodriguez Henry , Robles Ana I. , Hiltke Tara , Lewis Michael T. , Nangia Julie R. , Nemati Shafaee Maryam , Li Shunqiang , Hagemann Ian S. , Hoog Jeremy , Lim Bora , Osborne C. Kent , Mani D.R. , Gillette Michael A. , Zhang Bing , Echeverria Gloria V. , Miles George , Rimawi Mothaffar F. , Carr Steven A. , Ademuyiwa Foluso O. , Satpathy Shankha , Ellis Matthew J.
Published: April 2023

Supplementary Figure from Proteogenomic Markers of Chemotherapy Resistance and Response in Triple-Negative Breast Cancer
Supplementary Table S8 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

HPV42- and HPV16-E6 BioID.
Supplementary Table S5 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

FISH probes.
Supplementary Figure 6 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Authors: Yaeger Rona , Mezzadra Riccardo , Sinopoli Jenna , Bian Yu , Marasco Michelangelo , Kaplun Esther , Gao Yijun , Zhao HuiYong , Paula Arnaud Da Cruz , Zhu Yingjie , Perez Almudena Chaves , Chadalavada Kalyani , Tse Edison , Chowdhry Sudhir , Bowker Sydney , Chang Qing , Qeriqi Besnik , Weigelt Britta , Nanjangud Gouri J. , Berger Michael F. , Der-Torossian Hirak , Anderes Kenna , Socci Nicholas D. , Shia Jinru , Riely Gregory J. , Murciano-Goroff Yonina R. , Li Bob T. , Christensen James G. , Reis-Filho Jorge S. , Solit David B. , de Stanchina Elisa , Lowe Scott W. , Rosen Neal , Misale Sandra
Published: April 2023

C106 resistant cells drug withdrawal and Patient #12 MSK-Impact data
Supplementary Table S3 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

Viral genome coverage in ViroCap assay.
Supplementary Table S14 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

HPV42 genome structural variants.
Supplementary Figure 4 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Authors: Yaeger Rona , Mezzadra Riccardo , Sinopoli Jenna , Bian Yu , Marasco Michelangelo , Kaplun Esther , Gao Yijun , Zhao HuiYong , Paula Arnaud Da Cruz , Zhu Yingjie , Perez Almudena Chaves , Chadalavada Kalyani , Tse Edison , Chowdhry Sudhir , Bowker Sydney , Chang Qing , Qeriqi Besnik , Weigelt Britta , Nanjangud Gouri J. , Berger Michael F. , Der-Torossian Hirak , Anderes Kenna , Socci Nicholas D. , Shia Jinru , Riely Gregory J. , Murciano-Goroff Yonina R. , Li Bob T. , Christensen James G. , Reis-Filho Jorge S. , Solit David B. , de Stanchina Elisa , Lowe Scott W. , Rosen Neal , Misale Sandra
Published: April 2023

Generation of acquired resistance PDX model
Supplementary Table S13 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

HPV42 genome sequence comparison.
Supplementary Table S12 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

HPV42 consensus genomes.
Supplementary Table S11 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

DEG HPV+ vs. HPV- CESC/HNSCC.
Supplementary Table S10 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

HPV abundance scores TCGA.
Supplementary Table S1 from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

Sample-assay overview.
Supplementary Figure from Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness versus Lineage Output in Dnmt3a-Mutant Clonal Hematopoiesis
Authors: SanMiguel Jennifer M. , Eudy Elizabeth , Loberg Matthew A. , Young Kira A. , Mistry Jayna J. , Mujica Kristina D. , Schwartz Logan S. , Stearns Timothy M. , Challen Grant A. , Trowbridge Jennifer J.
Published: April 2023

Supplementary Figure from Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness versus Lineage Output in Dnmt3a-Mutant Clonal Hematopoiesis
Table S3 from OncoLoop: A Network-Based Precision Cancer Medicine Framework
Authors: Vasciaveo Alessandro , Arriaga Juan Martín , de Almeida Francisca Nunes , Zou Min , Douglass Eugene F. , Picech Florencia , Shibata Maho , Rodriguez-Calero Antonio , de Brot Simone , Mitrofanova Antonina , Chua Chee Wai , Karan Charles , Realubit Ronald , Pampou Sergey , Kim Jaime Y. , Afari Stephanie N. , Mukhammadov Timur , Zanella Luca , Corey Eva , Alvarez Mariano J. , Rubin Mark A. , Shen Michael M. , Califano Andrea , Abate-Shen Cory
Published: April 2023

Supplementary Table 3: Transcriptomic analyses of the human patient samples
A. TCGA Interactome
B. SU2C Interactome
C. Protein activity TCGA
D. Protein Activity SU2C
Supplementary Figures S1-S11 from OncoLoop: A Network-Based Precision Cancer Medicine Framework
Authors: Vasciaveo Alessandro , Arriaga Juan Martín , de Almeida Francisca Nunes , Zou Min , Douglass Eugene F. , Picech Florencia , Shibata Maho , Rodriguez-Calero Antonio , de Brot Simone , Mitrofanova Antonina , Chua Chee Wai , Karan Charles , Realubit Ronald , Pampou Sergey , Kim Jaime Y. , Afari Stephanie N. , Mukhammadov Timur , Zanella Luca , Corey Eva , Alvarez Mariano J. , Rubin Mark A. , Shen Michael M. , Califano Andrea , Abate-Shen Cory
Published: April 2023

Figure S1: Genomic alterations in prostate cancer represented in the GEMMs (related to Fig. 2).
Figure S2: Additional phenotypic analyses of the GEMMs (related to Fig. 2).
Figure S3: Phenotypic analysis of allograft and organoid models (related to Fig. 2).
Figure S4: Additional transcriptomic analyses of the GEMMs (related to Fig. 3).
Figure S5: Analyses of AR activity in GEMMS (related to Fig. 3).
Figure S6: Regulatory sub-networks of the GEMM clusters (related to Fig. 3).
Figure S7. MR-match of prostate cancer cells lines to human PCa (related to Figs. 5).
Figure S8. Drug perturbation protein activity profiles from DU145 cells (related to Figs. 5, 6, 7).
Figure S9. LNCaP Pharmacotyping to patients and GEMMs (related to Figs. 5).
Figure S10: Additional validation of drug candidates (related to Figs 6, 7).
Figure S11: Additional validation of drug candidates (related to Figs 6).
Supplementary Figure S5 from Efficacy of a Small-Molecule Inhibitor of KrasG12D in Immunocompetent Models of Pancreatic Cancer
Authors: Kemp Samantha B. , Cheng Noah , Markosyan Nune , Sor Rina , Kim Il-Kyu , Hallin Jill , Shoush Jason , Quinones Liz , Brown Natalie V. , Bassett Jared B. , Joshi Nikhil , Yuan Salina , Smith Molly , Vostrejs William P. , Perez-Vale Kia Z. , Kahn Benjamin , Mo Feiyan , Donahue Timothy R. , Radu Caius G. , Clendenin Cynthia , Christensen James G. , Vonderheide Robert H. , Stanger Ben Z.
Published: April 2023

MRTX1133 exerts in vivo effects early in treatment
Detailed Materials and Methods from OncoLoop: A Network-Based Precision Cancer Medicine Framework
Authors: Vasciaveo Alessandro , Arriaga Juan Martín , de Almeida Francisca Nunes , Zou Min , Douglass Eugene F. , Picech Florencia , Shibata Maho , Rodriguez-Calero Antonio , de Brot Simone , Mitrofanova Antonina , Chua Chee Wai , Karan Charles , Realubit Ronald , Pampou Sergey , Kim Jaime Y. , Afari Stephanie N. , Mukhammadov Timur , Zanella Luca , Corey Eva , Alvarez Mariano J. , Rubin Mark A. , Shen Michael M. , Califano Andrea , Abate-Shen Cory
Published: April 2023

Detailed Materials and Methods
Supplementary Figure S2 from Efficacy of a Small-Molecule Inhibitor of KrasG12D in Immunocompetent Models of Pancreatic Cancer
Authors: Kemp Samantha B. , Cheng Noah , Markosyan Nune , Sor Rina , Kim Il-Kyu , Hallin Jill , Shoush Jason , Quinones Liz , Brown Natalie V. , Bassett Jared B. , Joshi Nikhil , Yuan Salina , Smith Molly , Vostrejs William P. , Perez-Vale Kia Z. , Kahn Benjamin , Mo Feiyan , Donahue Timothy R. , Radu Caius G. , Clendenin Cynthia , Christensen James G. , Vonderheide Robert H. , Stanger Ben Z.
Published: April 2023

MRTX1133 is selective for KRASG12D in immunocompetent implantation tumor models
Supplementary Figure from Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma
Authors: Wu Lingxiang , Wu Wei , Zhang Junxia , Zhao Zheng , Li Liangyu , Zhu Mengyan , Wu Min , Wu Fan , Zhou Fengqi , Du Yuxin , Chai Rui-Chao , Zhang Wei , Qiu Xiaoguang , Liu Quanzhong , Wang Ziyu , Li Jie , Li Kening , Chen Apeng , Jiang Yinan , Xiao Xiangwei , Zou Han , Srivastava Rashmi , Zhang Tingting , Cai Yun , Liang Yuan , Huang Bin , Zhang Ruohan , Lin Fan , Hu Lang , Wang Xiuxing , Qian Xu , Lv Sali , Hu Baoli , Zheng Siyuan , Hu Zhibin , Shen Hongbing , You Yongping , Verhaak Roel G.W. , Jiang Tao , Wang Qianghu
Published: April 2023

Supplementary Figure from Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma
Supplementary Table 4 from A Molecular Switch between Mammalian MLL Complexes Dictates Response to Menin–MLL Inhibition
Authors: Soto-Feliciano Yadira M. , Sánchez-Rivera Francisco J. , Perner Florian , Barrows Douglas W. , Kastenhuber Edward R. , Ho Yu-Jui , Carroll Thomas , Xiong Yijun , Anand Disha , Soshnev Alexey A. , Gates Leah , Beytagh Mary Clare , Cheon David , Gu Shengqing , Liu X. Shirley , Krivtsov Andrei V. , Meneses Maximiliano , de Stanchina Elisa , Stone Richard M. , Armstrong Scott A. , Lowe Scott W. , Allis C. David
Published: April 2023

RNA-Seq results
Supplementary Table 1 from A Molecular Switch between Mammalian MLL Complexes Dictates Response to Menin–MLL Inhibition
Authors: Soto-Feliciano Yadira M. , Sánchez-Rivera Francisco J. , Perner Florian , Barrows Douglas W. , Kastenhuber Edward R. , Ho Yu-Jui , Carroll Thomas , Xiong Yijun , Anand Disha , Soshnev Alexey A. , Gates Leah , Beytagh Mary Clare , Cheon David , Gu Shengqing , Liu X. Shirley , Krivtsov Andrei V. , Meneses Maximiliano , de Stanchina Elisa , Stone Richard M. , Armstrong Scott A. , Lowe Scott W. , Allis C. David
Published: April 2023

Sequences of sgRNAs and primers
Supplementary Tables S1 and S2 from Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA
Authors: Cortes-Ciriano Isidro , Steele Christopher D. , Piculell Katherine , Al-Ibraheemi Alyaa , Eulo Vanessa , Bui Marilyn M. , Chatzipli Aikaterini , Dickson Brendan C. , Borcherding Dana C. , Feber Andrew , Galor Alon , Hart Jesse , Jones Kevin B. , Jordan Justin T. , Kim Raymond H. , Lindsay Daniel , Miller Colin , Nishida Yoshihiro , Proszek Paula Z. , Serrano Jonathan , Sundby R. Taylor , Szymanski Jeffrey J. , Ullrich Nicole J. , Viskochil David , Wang Xia , Snuderl Matija , Park Peter J. , Flanagan Adrienne M. , Hirbe Angela C. , Pillay Nischalan , Miller David T.
Published: April 2023

Supplementary Table 1 includes the metadata on all subjects, including basic demographics and medical history. Supplementary Table 2 provides statistics on chrom 8 gene expression among tumors with H3K27me3 loss.
Note: no changes have been made to this file since our last resubmission.
Supplementary Table S4 from Mutant NPM1 Hijacks Transcriptional Hubs to Maintain Pathogenic Gene Programs in Acute Myeloid Leukemia
Authors: Wang Xue Qing David , Fan Dandan , Han Qinyu , Liu Yiman , Miao Hongzhi , Wang Xinyu , Li Qinglan , Chen Dong , Gore Haley , Himadewi Pamela , Pfeifer Gerd P. , Cierpicki Tomasz , Grembecka Jolanta , Su Jianzhong , Chong Shasha , Wan Liling , Zhang Xiaotian
Published: April 2023

Supplemenary Table S4 shows the differential expressed genes in 25nM Selinexorvs DMSO treatment at 24hr in OCI-AML3-NPM1c-degron2 cells.
Supplementary Tables from Detecting Liver Cancer Using Cell-Free DNA Fragmentomes
Authors: Foda Zachariah H. , Annapragada Akshaya V. , Boyapati Kavya , Bruhm Daniel C. , Vulpescu Nicholas A. , Medina Jamie E. , Mathios Dimitrios , Cristiano Stephen , Niknafs Noushin , Luu Harry T. , Goggins Michael G. , Anders Robert A. , Sun Jing , Meta Shruti H. , Thomas David L. , Kirk Gregory D. , Adleff Vilmos , Phallen Jillian , Scharpf Robert B. , Kim Amy K. , Velculescu Victor E.
Published: April 2023

Supplementary Table S1 shows Clinical information of US/EU patients analyzed.
Supplementary Table S2 is a summary of whole genome cfDNA analyses.
Supplementary Table S3 shows clinical information of Hong Kong patients analyzed.
Supplementary Table S4 shows the lowest scoring transcription factors in US/EU cohort samples.
Supplementary Table S5 lists the plasma volume and cfDNA amounts used in genomic libraries.
Figure S2 from CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
Authors: Larson Sarah M. , Walthers Christopher M. , Ji Brenda , Ghafouri Sanaz N. , Naparstek Jacob , Trent Jacqueline , Chen Jia Ming , Roshandell Mobina , Harris Caitlin , Khericha Mobina , Schweppe Thomas , Berent-Maoz Beata , Gosliner Stanley B. , Almaktari Amr , Ceja Melanie Ayala , Allen-Auerbach Martin S. , Said Jonathan , Nawaly Karla , Mead Monica , de Vos Sven , Young Patricia A. , Oliai Caspian , Schiller Gary J. , Timmerman John M. , Ribas Antoni , Chen Yvonne Y.
Published: April 2023

CD14/CD20 depletion did not significantly alter regulatory T (Treg) cell content in CART19/20 cell product and in patient peripheral blood post infusion. Intracellular staining of starting (unactivated) TN/MEM population, CART19/20 final product, and patient PBMC collected 14 days post CART19/20 infusion. FOXP3+ frequency is shown as a percentage of CD3+CD4+ T cells.
Figure S8 from LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma
Authors: Stein Benjamin D. , Ferrarone John R. , Gardner Eric E. , Chang Jae Won , Wu David , Hollstein Pablo E. , Liang Roger J. , Yuan Min , Chen Qiuying , Coukos John S. , Sindelar Miriam , Ngo Bryan , Gross Steven S. , Shaw Reuben J. , Zhang Chen , Asara John M. , Moellering Raymond E. , Varmus Harold , Cantley Lewis C.
Published: April 2023

Figure S8. Tpi1 inactivation in KL autochthonous tumor model alters histology and pathology.
Figure S4 from LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma
Authors: Stein Benjamin D. , Ferrarone John R. , Gardner Eric E. , Chang Jae Won , Wu David , Hollstein Pablo E. , Liang Roger J. , Yuan Min , Chen Qiuying , Coukos John S. , Sindelar Miriam , Ngo Bryan , Gross Steven S. , Shaw Reuben J. , Zhang Chen , Asara John M. , Moellering Raymond E. , Varmus Harold , Cantley Lewis C.
Published: April 2023

Figure S4. Members of the salt Inducible kinase family phosphorylate TPI1.
Figure S3 from LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma
Authors: Stein Benjamin D. , Ferrarone John R. , Gardner Eric E. , Chang Jae Won , Wu David , Hollstein Pablo E. , Liang Roger J. , Yuan Min , Chen Qiuying , Coukos John S. , Sindelar Miriam , Ngo Bryan , Gross Steven S. , Shaw Reuben J. , Zhang Chen , Asara John M. , Moellering Raymond E. , Varmus Harold , Cantley Lewis C.
Published: April 2023

Figure S3. TPI1 phosphorylation regulates triose phosphate levels and metabolic flux.
Figure S2 from LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma
Authors: Stein Benjamin D. , Ferrarone John R. , Gardner Eric E. , Chang Jae Won , Wu David , Hollstein Pablo E. , Liang Roger J. , Yuan Min , Chen Qiuying , Coukos John S. , Sindelar Miriam , Ngo Bryan , Gross Steven S. , Shaw Reuben J. , Zhang Chen , Asara John M. , Moellering Raymond E. , Varmus Harold , Cantley Lewis C.
Published: April 2023

Figure S2. Phosphorylation of human TPI1 is LKB1-dependent.
Figure S4 from Extrachromosomal DNA Amplification Contributes to Small Cell Lung Cancer Heterogeneity and Is Associated with Worse Outcomes
Authors: Pongor Lőrinc Sándor , Schultz Christopher W. , Rinaldi Lorenzo , Wangsa Darawalee , Redon Christophe E. , Takahashi Nobuyuki , Fialkoff Gavriel , Desai Parth , Zhang Yang , Burkett Sandra , Hermoni Nadav , Vilk Noa , Gutin Jenia , Gergely Rona , Zhao Yongmei , Nichols Samantha , Vilimas Rasa , Sciuto Linda , Graham Chante , Caravaca Juan Manuel , Turan Sevilay , Tsai-wei Shen , Rajapakse Vinodh N. , Kumar Rajesh , Upadhyay Deep , Kumar Suresh , Kim Yoo Sun , Roper Nitin , Tran Bao , Hewitt Stephen M. , Kleiner David E. , Aladjem Mirit I. , Friedman Nir , Hager Gordon L. , Pommier Yves , Ried Thomas , Thomas Anish
Published: April 2023

ecDNA heterogeneity in SCLC, related to Figure 4
Supplementary Table S3 from Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma
Authors: Danlos François-Xavier , Texier Matthieu , Job Bastien , Mouraud Severine , Cassard Lydie , Baldini Capucine , Varga Andrea , Yurchenko Andrey A. , Rabeau Audrey , Champiat Stéphane , Letourneur Diane , Bredel Delphine , Susini Sandrine , Blum Yuna , Parpaleix Aurelien , Parlavecchio Cedric , Tselikas Lambros , Fahrner Jean-Eudes , Goubet Anne-Gaelle , Rouanne Mathieu , Rafie Saloomeh , Abbassi Alae , Kasraoui Ines , Breckler Marie , Farhane Siham , Ammari Samy , Laghouati Salim , Gazzah Anas , Lacroix Ludovic , Besse Benjamin , Droin Nathalie , Deloger Marc , Cotteret Sophie , Adam Julien , Zitvogel Laurence , Nikolaev Sergey I. , Chaput Nathalie , Massard Christophe , Soria Jean-Charles , Gomez-Roca Carlos , Zalcman Gerard , Planchard David , Marabelle Aurelien
Published: April 2023

Adverse events emergent during treatment and related to experimental drugs by the investigators according to CTCAE Version 4.03.
Supplementary Table S2 from Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma
Authors: Danlos François-Xavier , Texier Matthieu , Job Bastien , Mouraud Severine , Cassard Lydie , Baldini Capucine , Varga Andrea , Yurchenko Andrey A. , Rabeau Audrey , Champiat Stéphane , Letourneur Diane , Bredel Delphine , Susini Sandrine , Blum Yuna , Parpaleix Aurelien , Parlavecchio Cedric , Tselikas Lambros , Fahrner Jean-Eudes , Goubet Anne-Gaelle , Rouanne Mathieu , Rafie Saloomeh , Abbassi Alae , Kasraoui Ines , Breckler Marie , Farhane Siham , Ammari Samy , Laghouati Salim , Gazzah Anas , Lacroix Ludovic , Besse Benjamin , Droin Nathalie , Deloger Marc , Cotteret Sophie , Adam Julien , Zitvogel Laurence , Nikolaev Sergey I. , Chaput Nathalie , Massard Christophe , Soria Jean-Charles , Gomez-Roca Carlos , Zalcman Gerard , Planchard David , Marabelle Aurelien
Published: April 2023

Treatment and dose modifications in patients according to their DCB status.
Supplementary Figure S6 from Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma
Authors: Danlos François-Xavier , Texier Matthieu , Job Bastien , Mouraud Severine , Cassard Lydie , Baldini Capucine , Varga Andrea , Yurchenko Andrey A. , Rabeau Audrey , Champiat Stéphane , Letourneur Diane , Bredel Delphine , Susini Sandrine , Blum Yuna , Parpaleix Aurelien , Parlavecchio Cedric , Tselikas Lambros , Fahrner Jean-Eudes , Goubet Anne-Gaelle , Rouanne Mathieu , Rafie Saloomeh , Abbassi Alae , Kasraoui Ines , Breckler Marie , Farhane Siham , Ammari Samy , Laghouati Salim , Gazzah Anas , Lacroix Ludovic , Besse Benjamin , Droin Nathalie , Deloger Marc , Cotteret Sophie , Adam Julien , Zitvogel Laurence , Nikolaev Sergey I. , Chaput Nathalie , Massard Christophe , Soria Jean-Charles , Gomez-Roca Carlos , Zalcman Gerard , Planchard David , Marabelle Aurelien
Published: April 2023

Cytotoxic response in tumor biopsies of patients with No DCB upon combination treatment.
Supplemental Figure S4 from Targeting Microglial Metabolic Rewiring Synergizes with Immune-Checkpoint Blockade Therapy for Glioblastoma
Authors: Ye Zengpanpan , Ai Xiaolin , Yang Kailin , Yang Zhengnan , Fei Fan , Liao Xiaoling , Qiu Zhixin , Gimple Ryan C. , Yuan Huairui , Huang Hao , Gong Yanqiu , Xiao Chaoxin , Yue Jing , Huang Liang , Saulnier Olivier , Wang Wei , Zhang Peidong , Dai Lunzhi , Wang Xin , Wang Xiuxing , Ahn Young Ha , You Chao , Xu Jianguo , Wan Xiaoxiao , Taylor Michael D. , Zhao Linjie , Rich Jeremy N. , Zhou Shengtao
Published: April 2023

Supplemental Figure S4 describes that NR4A2-knockdown affects lipid metabolism and promotes antigen presentation of microglia.
Data from A Molecularly Annotated Platform of Patient-Derived Xenografts (“Xenopatients”) Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer
Authors: Bertotti Andrea , Migliardi Giorgia , Galimi Francesco , Sassi Francesco , Torti Davide , Isella Claudio , Corà Davide , Di Nicolantonio Federica , Buscarino Michela , Petti Consalvo , Ribero Dario , Russolillo Nadia , Muratore Andrea , Massucco Paolo , Pisacane Alberto , Molinaro Luca , Valtorta Emanuele , Sartore-Bianchi Andrea , Risio Mauro , Capussotti Lorenzo , Gambacorta Marcello , Siena Salvatore , Medico Enzo , Sapino Anna , Marsoni Silvia , Comoglio Paolo M. , Bardelli Alberto , Trusolino Livio
Published: April 2023

Abstract
Only a fraction of patients with metastatic colorectal cancer receive clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) antibodies, which calls for the identification of novel biomarkers for better personalized medicine. We produced large xenograft cohorts from 85 patient-derived, genetically characterized metastatic colorectal cancer samples (“xenopatients”) to discover novel determinants of therapeutic response and new oncoprotein targets. Serially passaged tumors retained the morphologic and genomic features of their original counterparts. A validation trial confirmed the robustness of this approach: xenopatients responded to the anti-EGFR antibody cetuximab with rates and extents analogous to those observed in the clinic and could be prospectively stratified as responders or nonresponders on the basis of several predictive biomarkers. Genotype–response correlations indicated HER2 amplification specifically in a subset of cetuximab-resistant, KRAS/NRAS/BRAF/PIK3CA wild-type cases. Importantly, HER2 amplification was also enriched in clinically nonresponsive KRAS wild-type patients. A proof-of-concept, multiarm study in HER2-amplified xenopatients revealed that the combined inhibition of HER2 and EGFR induced overt, long-lasting tumor regression. Our results suggest promising therapeutic opportunities in cetuximab-resistant patients with metastatic colorectal cancer, whose medical treatment in the chemorefractory setting remains an unmet clinical need.

Significance: Direct transfer xenografts of tumor surgical specimens conserve the interindividual diversity and the genetic heterogeneity typical of the tumors of origin, combining the flexibility of preclinical analysis with the informative value of population-based studies. Our suite of patient-derived xenografts from metastatic colorectal carcinomas reliably mimicked disease response in humans, prospectively recapitulated biomarker-based case stratification, and identified HER2 as a predictor of resistance to anti-epidermal growth factor receptor antibodies and of response to combination therapies against HER2 and epidermal growth factor receptor in this tumor setting. Cancer Discovery; 1(6); 508–23. ©2011 AACR.

Read the Commentary on this article by Ciardiello and Normanno, p. 472

This article is highlighted in the In This Issue feature, p. 457
Data from Modulation of Activation-Loop Phosphorylation by JAK Inhibitors Is Binding Mode Dependent
Authors: Andraos Rita , Qian Zhiyan , Bonenfant Débora , Rubert Joëlle , Vangrevelinghe Eric , Scheufler Clemens , Marque Fanny , Régnier Catherine H. , De Pover Alain , Ryckelynck Hugues , Bhagwat Neha , Koppikar Priya , Goel Aviva , Wyder Lorenza , Tavares Gisele , Baffert Fabienne , Pissot-Soldermann Carole , Manley Paul W. , Gaul Christoph , Voshol Hans , Levine Ross L. , Sellers William R. , Hofmann Francesco , Radimerski Thomas
Published: April 2023

Abstract
Janus kinase (JAK) inhibitors are being developed for the treatment of rheumatoid arthritis, psoriasis, myeloproliferative neoplasms, and leukemias. Most of these drugs target the ATP-binding pocket and stabilize the active conformation of the JAK kinases. This type I binding mode can lead to an increase in JAK activation loop phosphorylation, despite blockade of kinase function. Here we report that stabilizing the inactive state via type II inhibition acts in the opposite manner, leading to a loss of activation loop phosphorylation. We used X-ray crystallography to corroborate the binding mode and report for the first time the crystal structure of the JAK2 kinase domain in an inactive conformation. Importantly, JAK inhibitor–induced activation loop phosphorylation requires receptor interaction, as well as intact kinase and pseudokinase domains. Hence, depending on the respective conformation stabilized by a JAK inhibitor, hyperphosphorylation of the activation loop may or may not be elicited.

Significance: This study shows that JAK inhibitors can lead to an increase of activation loop phosphorylation in a manner that is binding mode dependent. Our results highlight the need for detailed understanding of inhibitor mechanism of action, and that it may be possible to devise strategies that avoid target priming using alternative modes of inhibiting JAK kinase activity for the treatment of JAK-dependent diseases. Cancer Discov; 2(6); 512–23. © 2012 AACR.

This article is highlighted in the In This Issue feature, p. 473
Data from A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors
Authors: Jahchan Nadine S. , Dudley Joel T. , Mazur Pawel K. , Flores Natasha , Yang Dian , Palmerton Alec , Zmoos Anne-Flore , Vaka Dedeepya , Tran Kim Q.T. , Zhou Margaret , Krasinska Karolina , Riess Jonathan W. , Neal Joel W. , Khatri Purvesh , Park Kwon S. , Butte Atul J. , Sage Julien
Published: April 2023

Abstract
Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)–approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein–coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma. These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs.

Significance: Our work shows the power of bioinformatics-based drug approaches to rapidly repurpose FDA-approved drugs and identifies a novel class of molecules to treat patients with SCLC, a cancer for which no effective novel systemic treatments have been identified in several decades. In addition, our experiments highlight the importance of novel autocrine mechanisms in promoting the growth of neuroendocrine tumor cells. Cancer Discov; 3(12); 1364–77. ©2013 AACR.

See related commentary by Wang and Byers, p. 1333

This article is highlighted in the In This Issue feature, p. 1317
Data from A Central Role for RAF→MEK→ERK Signaling in the Genesis of Pancreatic Ductal Adenocarcinoma
Authors: Collisson Eric A. , Trejo Christy L. , Silva Jillian M. , Gu Shenda , Korkola James E. , Heiser Laura M. , Charles Roch-Philippe , Rabinovich Brian A. , Hann Byron , Dankort David , Spellman Paul T. , Phillips Wayne A. , Gray Joe W. , McMahon Martin
Published: April 2023

Abstract
KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDA) but remains an intractable pharmacologic target. Consequently, defining RAS effector pathway(s) required for PDA initiation and maintenance is critical to improve treatment of this disease. Here, we show that expression of BRAFV600E, but not PIK3CAH1047R, in the mouse pancreas leads to pancreatic intraepithelial neoplasia (PanIN) lesions. Moreover, concomitant expression of BRAFV600E and TP53R270H result in lethal PDA. We tested pharmacologic inhibitors of RAS effectors against multiple human PDA cell lines. Mitogen-activated protein (MAP)/extracellular signal–regulated (ERK) kinase (MEK) inhibition was highly effective both in vivo and in vitro and was synergistic with AKT inhibition in most cell lines tested. We show that RAF→MEK→ERK signaling is central to the initiation and maintenance of PDA and to rational combination strategies in this disease. These results emphasize the value of leveraging multiple complementary experimental systems to prioritize pathways for effective intervention strategies in PDA.

Significance: PDA is difficult to treat, in large part, due to recurrent mutations in the KRAS gene. Here, we define rational treatment approaches for the disease achievable today with existing drug combinations by thorough genetic and pharmacologic dissection of the major KRAS effector pathways, RAF→MEK→ERK and phosphoinositide 3′-kinase (PI3′K)→AKT. Cancer Discov; 2(8); 685–93. ©2012 AACR.

Read the Commentary on this article by Hanrahan et al., p. 666.

This article is highlighted in the In This Issue feature, p. 653.
Data from Loss of 53BP1 Causes PARP Inhibitor Resistance in Brca1-Mutated Mouse Mammary Tumors
Authors: Jaspers Janneke E. , Kersbergen Ariena , Boon Ute , Sol Wendy , van Deemter Liesbeth , Zander Serge A. , Drost Rinske , Wientjens Ellen , Ji Jiuping , Aly Amal , Doroshow James H. , Cranston Aaron , Martin Niall M.B. , Lau Alan , O'Connor Mark J. , Ganesan Shridar , Borst Piet , Jonkers Jos , Rottenberg Sven
Published: April 2023

Abstract
Inhibition of PARP is a promising therapeutic strategy for homologous recombination–deficient tumors, such as BRCA1-associated cancers. We previously reported that BRCA1-deficient mouse mammary tumors may acquire resistance to the clinical PARP inhibitor (PARPi) olaparib through activation of the P-glycoprotein drug efflux transporter. Here, we show that tumor-specific genetic inactivation of P-glycoprotein increases the long-term response of BRCA1-deficient mouse mammary tumors to olaparib, but these tumors eventually developed PARPi resistance. In a fraction of cases, this resistance is caused by partial restoration of homologous recombination due to somatic loss of 53BP1. Importantly, PARPi resistance was minimized by long-term treatment with the novel PARP inhibitor AZD2461, which is a poor P-glycoprotein substrate. Together, our data suggest that restoration of homologous recombination is an important mechanism for PARPi resistance in BRCA1-deficient mammary tumors and that the risk of relapse of BRCA1-deficient tumors can be effectively minimized by using optimized PARP inhibitors.

Significance: In this study, we show that loss of 53BP1 causes resistance to PARP inhibition in mouse mammary tumors that are deficient in BRCA1. We hypothesize that low expression or absence of 53BP1 also reduces the response of patients with BRCA1-deficient tumors to PARP inhibitors. Cancer Discov; 3(1); 68–81. ©2012 AACR.

See related commentary by Fojo and Bates, p. 20

This article is highlighted in the In This Issue feature, p. 1