bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figures S1 - S7, Tables S1 - S2 from Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120
Authors: Chen Shih-Hsun , Zhang Youyan , Van Horn Robert D. , Yin Tinggui , Buchanan Sean , Yadav Vipin , Mochalkin Igor , Wong Swee Seong , Yue Yong Gang , Huber Lysiane , Conti Ilaria , Henry James R. , Starling James J. , Plowman Gregory D. , Peng Sheng-Bin
Published: April 2023

Supplementary Figure S1. Validation of BRAF deletion in BxPC-3 cells by Sanger's sequencing method. Supplementary Figure S2. BRAF deletion (deltaBRAF), but not WT BRAF, is able to transform cells. Supplementary Figure S3. Validation of in situ PLA in HeLa and HEK293 cells. Supplementary Figure S4. Phospho-CRAF and MAPK activation in selected tumor cells with BRAF alteration or KRAS mutation. Supplementary Figure S5. Phospho-MEK and ERK inhibition by dabrafenib in tumor cells harboring BRAF deletion. Supplementary Figure S6. In vitro effects of MAPK inhibitors on tumor cells harboring BRAF deletions. Supplementary Table S1. Novel somatic BRAF in-frame deletions from cancer cell lines and patient samples. Supplementary Figure S7. LY3009120, but not vemurafenib, exhibited significant tumor growth inhibition and regression in lung and pancreatic tumor xenograft models harboring the BRAF deletions without significant body weight loss. Supplementary Table S2. IC50 of LY3009120 and vemurafenib against tumor cells with atypical BRAF mutations.
Supplementary Table S4 from BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Authors: Tasdemir Nilgun , Banito Ana , Roe Jae-Seok , Alonso-Curbelo Direna , Camiolo Matthew , Tschaharganeh Darjus F. , Huang Chun-Hao , Aksoy Ozlem , Bolden Jessica E. , Chen Chi-Chao , Fennell Myles , Thapar Vishal , Chicas Agustin , Vakoc Christopher R. , Lowe Scott W.
Published: April 2023

Sequences of shRNAs and qRT-PCR primers.
Supplementary Table S3 from BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Authors: Tasdemir Nilgun , Banito Ana , Roe Jae-Seok , Alonso-Curbelo Direna , Camiolo Matthew , Tschaharganeh Darjus F. , Huang Chun-Hao , Aksoy Ozlem , Bolden Jessica E. , Chen Chi-Chao , Fennell Myles , Thapar Vishal , Chicas Agustin , Vakoc Christopher R. , Lowe Scott W.
Published: April 2023

Lists of gene signatures from RNA-Seq analysis.
Supplementary Table 5 from A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma
Authors: Mirabello Lisa , Koster Roelof , Moriarity Branden S. , Spector Logan G. , Meltzer Paul S. , Gary Joy , Machiela Mitchell J. , Pankratz Nathan , Panagiotou Orestis A. , Largaespada David , Wang Zhaoming , Gastier-Foster Julie M. , Gorlick Richard , Khanna Chand , de Toledo Silvia Regina Caminada , Petrilli Antonio S. , Patiño-Garcia Ana , Sierrasesúmaga Luis , Lecanda Fernando , Andrulis Irene L. , Wunder Jay S. , Gokgoz Nalan , Serra Massimo , Hattinger Claudia , Picci Piero , Scotlandi Katia , Flanagan Adrienne M. , Tirabosco Roberto , Amary Maria Fernanda , Halai Dina , Ballinger Mandy L. , Thomas David M. , Davis Sean , Barkauskas Donald A. , Marina Neyssa , Helman Lee , Otto George M. , Becklin Kelsie L. , Wolf Natalie K. , Weg Madison T. , Tucker Margaret , Wacholder Sholom , Fraumeni Joseph F. , Caporaso Neil E. , Boland Joseph F. , Hicks Belynda D. , Vogt Aurelie , Burdett Laurie , Yeager Meredith , Hoover Robert N. , Chanock Stephen J. , Savage Sharon A.
Published: April 2023

Top genotyped SNP associations with metastasis at diagnosis in the discovery and all replication studies.
Supplementary Table S5 from CRISPR Screens Provide a Comprehensive Assessment of Cancer Vulnerabilities but Generate False-Positive Hits for Highly Amplified Genomic Regions
Authors: Munoz Diana M. , Cassiani Pamela J. , Li Li , Billy Eric , Korn Joshua M. , Jones Michael D. , Golji Javad , Ruddy David A. , Yu Kristine , McAllister Gregory , DeWeck Antoine , Abramowski Dorothee , Wan Jessica , Shirley Matthew D. , Neshat Sarah Y. , Rakiec Daniel , de Beaumont Rosalie , Weber Odile , Kauffmann Audrey , McDonald E. Robert , Keen Nicholas , Hofmann Francesco , Sellers William R. , Schmelzle Tobias , Stegmeier Frank , Schlabach Michael R.
Published: April 2023

Locus-specific primer pairs.
Supplementary Tables 1 - 6, Figures 1 - 7 from Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 “Gatekeeper” F691L Mutation with PLX3397
Authors: Smith Catherine C. , Zhang Chao , Lin Kimberly C. , Lasater Elisabeth A. , Zhang Ying , Massi Evan , Damon Lauren E. , Pendleton Matthew , Bashir Ali , Sebra Robert , Perl Alexander , Kasarskis Andrew , Shellooe Rafe , Tsang Garson , Carias Heidi , Powell Ben , Burton Elizabeth A. , Matusow Bernice , Zhang Jiazhong , Spevak Wayne , Ibrahim Prabha N. , Le Mai H. , Hsu Henry H. , Habets Gaston , West Brian L. , Bollag Gideon , Shah Neil P.
Published: April 2023

Supplementary Table 1. Crystallographic Data and Refinement statistics. Supplementary Table 2. Comparing Target Inhibition by Quizartinib and PLX3397 in Engineered Ba/F3 cells Expressing FLT3-ITD, FLT3-ITD/F691L and FLT3-ITD/D835Y. Supplementary Table 3. Inhibitory Concentration (IC50) for Proliferation of Human Leukemia Cell Lines in PLX3397. Supplementary Table 4. 48 Hour Inhibitory Concentration (IC50) for Proliferation of Ba/F3 Cells Expressing Quizartinib and PLX3397-Resistant FLT3-ITD Mutant Isoforms. Supplementary Table 5. Patient Characteristics. Supplementary Table 6. Low Frequency FLT3 Kinase Domain Mutations of Uncertain Significance Observed at the Time of Resistance in Patient 1.14. Supplementary Figure 1. Composite omit map contoured at 1sigma level for the bound quizartinib and a structural water molecule. Supplementary Figure 2. Comparing the actual and previously predicted binding modes of quizartinib. Supplementary Figure 3. Structural model showing that D835 induces the DFG-in conformation of the activation loop, resulting in an orientation of F830 that precludes quizartinib binding. Supplementary Figure 4. Structural superposition of quizartinib (green) and PLX3397 (orange) highlighting the key structural difference responsible for their different susceptibilities to L691. Supplementary Figure 5. PLX3397 Inhibits FLT3 Signaling In Vitro. Supplementary Figure 6. Molm14 F691L Cells Demonstrate Resistance to Quizartinib. Supplementary Figure 7. Activity of PLX3397Against Quizartinib Resistance-Causing FLT3-ITD Kinase Domain Mutations.
Supplementary Figures S1 - S11 from CRISPR Screens Provide a Comprehensive Assessment of Cancer Vulnerabilities but Generate False-Positive Hits for Highly Amplified Genomic Regions
Authors: Munoz Diana M. , Cassiani Pamela J. , Li Li , Billy Eric , Korn Joshua M. , Jones Michael D. , Golji Javad , Ruddy David A. , Yu Kristine , McAllister Gregory , DeWeck Antoine , Abramowski Dorothee , Wan Jessica , Shirley Matthew D. , Neshat Sarah Y. , Rakiec Daniel , de Beaumont Rosalie , Weber Odile , Kauffmann Audrey , McDonald E. Robert , Keen Nicholas , Hofmann Francesco , Sellers William R. , Schmelzle Tobias , Stegmeier Frank , Schlabach Michael R.
Published: April 2023

Supplementary Figure S1. Comparison of drop out phenotypes in MKN45, RKO, HT1080 highlighting selected pan-lethal genes. Supplementary Figure S2. The genes that scored as lethal by both RNAi and CRISPR were strongly enriched for known essential genes classes. Supplementary Figure S3. To identify likely off-target hits the lethality scores of non-expressed genes were examined, as they are expected not to be required for cell viability. Supplementary Figure S4. shRNAs directed towards CDK9 do not show robust protein depletion. Supplementary Figure S5. Additional methods measuring the proliferation effects of individual sgRNA/shRNAs to validate the impact that targeting selected genetic dependencies have on cell viability. Supplementary Figure S6. Correlation analysis displaying features that correlated most significantly with sgRNA potency. Supplementary Figure S7. Effect of relative position within a gene on sgRNA viability effects. Supplementary Figure S8. Non-scoring sgRNA in conserved Pfam domains have a reduced editing efficiency compared to guides with strong viability effects. Supplementary Figure S9. Multiple genomic cuts result in DNA damage induced G2/M cell cycle arrest. Supplementary Figure S10. Multiple genomic cuts lead to an increase in cell death. Supplementary Figure S11. Pie chart demonstrating that the overall contribution of copy number effects in determining essential genes in aneuploid lines is relatively minor.
Supplementary Figure Legends, Table Legends from CRISPR Screens Provide a Comprehensive Assessment of Cancer Vulnerabilities but Generate False-Positive Hits for Highly Amplified Genomic Regions
Authors: Munoz Diana M. , Cassiani Pamela J. , Li Li , Billy Eric , Korn Joshua M. , Jones Michael D. , Golji Javad , Ruddy David A. , Yu Kristine , McAllister Gregory , DeWeck Antoine , Abramowski Dorothee , Wan Jessica , Shirley Matthew D. , Neshat Sarah Y. , Rakiec Daniel , de Beaumont Rosalie , Weber Odile , Kauffmann Audrey , McDonald E. Robert , Keen Nicholas , Hofmann Francesco , Sellers William R. , Schmelzle Tobias , Stegmeier Frank , Schlabach Michael R.
Published: April 2023

Supplementary Figure Legends, Table Legends
Supplementary Table S4 from CD38-Mediated Immunosuppression as a Mechanism of Tumor Cell Escape from PD-1/PD-L1 Blockade
Authors: Chen Limo , Diao Lixia , Yang Yongbin , Yi Xiaohui , Rodriguez B. Leticia , Li Yanli , Villalobos Pamela A. , Cascone Tina , Liu Xi , Tan Lin , Lorenzi Philip L. , Huang Anfei , Zhao Qiang , Peng Di , Fradette Jared J. , Peng David H. , Ungewiss Christin , Roybal Jonathon , Tong Pan , Oba Junna , Skoulidis Ferdinandos , Peng Weiyi , Carter Brett W. , Gay Carl M. , Fan Youhong , Class Caleb A. , Zhu Jingfen , Rodriguez-Canales Jaime , Kawakami Masanori , Byers Lauren Averett , Woodman Scott E. , Papadimitrakopoulou Vassiliki A. , Dmitrovsky Ethan , Wang Jing , Ullrich Stephen E. , Wistuba Ignacio I. , Heymach John V. , Qin F. Xiao-Feng , Gibbons Don L.
Published: April 2023

Top 100 downregulated genes after anti-PD-L1 treatment.
Supplementary Data from A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105
Authors: Drilon Alexander , Fu Siqing , Patel Manish R. , Fakih Marwan , Wang Ding , Olszanski Anthony J. , Morgensztern Daniel , Liu Stephen V. , Cho Byoung Chul , Bazhenova Lyudmila , Rodriguez Cristina P. , Doebele Robert C. , Wozniak Antoinette , Reckamp Karen L. , Seery Tara , Nikolinakos Petros , Hu Zheyi , Oliver Jennifer W. , Trone Denise , McArthur Katherine , Patel Rupal , Multani Pratik S. , Ahn Myung-Ju
Published: April 2023

Figure S1, Figure S2, Figure S3, Figure S4, Table S1, Table S2, Table S3
Figure S4 from Endothelial Activation and Blood–Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells
Authors: Gust Juliane , Hay Kevin A. , Hanafi Laïla-Aïcha , Li Daniel , Myerson David , Gonzalez-Cuyar Luis F. , Yeung Cecilia , Liles W. Conrad , Wurfel Mark , Lopez Jose A. , Chen Junmei , Chung Dominic , Harju-Baker Susanna , Özpolat Tahsin , Fink Kathleen R. , Riddell Stanley R. , Maloney David G. , Turtle Cameron J.
Published: April 2023

Supplementary Figure 4. Activation of HUVECs by serum from patients with neurotoxicity.
Figure S1 from Endothelial Activation and Blood–Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells
Authors: Gust Juliane , Hay Kevin A. , Hanafi Laïla-Aïcha , Li Daniel , Myerson David , Gonzalez-Cuyar Luis F. , Yeung Cecilia , Liles W. Conrad , Wurfel Mark , Lopez Jose A. , Chen Junmei , Chung Dominic , Harju-Baker Susanna , Özpolat Tahsin , Fink Kathleen R. , Riddell Stanley R. , Maloney David G. , Turtle Cameron J.
Published: April 2023

Supplementary Figure 1. Treatment of neurotoxicity
Supplementary Methods from MACROD2 Haploinsufficiency Impairs Catalytic Activity of PARP1 and Promotes Chromosome Instability and Growth of Intestinal Tumors
Authors: Sakthianandeswaren Anuratha , Parsons Marie J. , Mouradov Dmitri , MacKinnon Ruth N. , Catimel Bruno , Liu Sheng , Palmieri Michelle , Love Christopher , Jorissen Robert N. , Li Shan , Whitehead Lachlan , Putoczki Tracy L. , Preaudet Adele , Tsui Cary , Nowell Cameron J. , Ward Robyn L. , Hawkins Nicholas J. , Desai Jayesh , Gibbs Peter , Ernst Matthias , Street Ian , Buchert Michael , Sieber Oliver M.
Published: April 2023

Supplementary Methods for generation of CRISPR and stable cell lines, MACROD2 mutation detection, QRT-PCR, phenotyping of MACROD2/APCmin mice, IHC, WB, TCF reporter assay, RNAseq analysis, generation of MACROD2 antibody, clonogenic assay, PARP1 activity assay, apoptosis assays, IF and FACS analysis.
Table S3 from BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Authors: Lin Kevin K. , Harrell Maria I. , Oza Amit M. , Oaknin Ana , Ray-Coquard Isabelle , Tinker Anna V. , Helman Elena , Radke Marc R. , Say Carmen , Vo Lan-Thanh , Mann Elaina , Isaacson Jeffrey D. , Maloney Lara , O'Malley David M. , Chambers Setsuko K. , Kaufmann Scott H. , Scott Clare L. , Konecny Gottfried E. , Coleman Robert L. , Sun James X. , Giordano Heidi , Brenton James D. , Harding Thomas C. , McNeish Iain A. , Swisher Elizabeth M.
Published: April 2023

Table S3 shows a summary of BRCA reversion mutations detected in postprogression circulating cell-free DNA
Figure S4 from In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma
Authors: Li Fei , Huang Qingyuan , Luster Troy A. , Hu Hai , Zhang Hua , Ng Wai-Lung , Khodadadi-Jamayran Alireza , Wang Wei , Chen Ting , Deng Jiehui , Ranieri Michela , Fang Zhaoyuan , Pyon Val , Dowling Catríona M. , Bagdatlioglu Ece , Almonte Christina , Labbe Kristen , Silver Heather , Rabin Alexandra R. , Jani Kandarp , Tsirigos Aristotelis , Papagiannakopoulos Thales , Hammerman Peter S. , Velcheti Vamsidhar , Freeman Gordon J. , Qi Jun , Miller George , Wong Kwok-Kin
Published: April 2023

Loss of Asf1a shows no significant effect on DNA damage and tumor cell proliferation
Figure S3 from In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma
Authors: Li Fei , Huang Qingyuan , Luster Troy A. , Hu Hai , Zhang Hua , Ng Wai-Lung , Khodadadi-Jamayran Alireza , Wang Wei , Chen Ting , Deng Jiehui , Ranieri Michela , Fang Zhaoyuan , Pyon Val , Dowling Catríona M. , Bagdatlioglu Ece , Almonte Christina , Labbe Kristen , Silver Heather , Rabin Alexandra R. , Jani Kandarp , Tsirigos Aristotelis , Papagiannakopoulos Thales , Hammerman Peter S. , Velcheti Vamsidhar , Freeman Gordon J. , Qi Jun , Miller George , Wong Kwok-Kin
Published: April 2023

CRISPR screen to identify targets regulating the natural host antitumor response
Figure S14 from In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma
Authors: Li Fei , Huang Qingyuan , Luster Troy A. , Hu Hai , Zhang Hua , Ng Wai-Lung , Khodadadi-Jamayran Alireza , Wang Wei , Chen Ting , Deng Jiehui , Ranieri Michela , Fang Zhaoyuan , Pyon Val , Dowling Catríona M. , Bagdatlioglu Ece , Almonte Christina , Labbe Kristen , Silver Heather , Rabin Alexandra R. , Jani Kandarp , Tsirigos Aristotelis , Papagiannakopoulos Thales , Hammerman Peter S. , Velcheti Vamsidhar , Freeman Gordon J. , Qi Jun , Miller George , Wong Kwok-Kin
Published: April 2023

In vivo F4/80 or GM-CSF blockade attenuates anti-tumor immune response in Asf1a KO and anti-PD-1 combination therapy
Figure S11 from In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma
Authors: Li Fei , Huang Qingyuan , Luster Troy A. , Hu Hai , Zhang Hua , Ng Wai-Lung , Khodadadi-Jamayran Alireza , Wang Wei , Chen Ting , Deng Jiehui , Ranieri Michela , Fang Zhaoyuan , Pyon Val , Dowling Catríona M. , Bagdatlioglu Ece , Almonte Christina , Labbe Kristen , Silver Heather , Rabin Alexandra R. , Jani Kandarp , Tsirigos Aristotelis , Papagiannakopoulos Thales , Hammerman Peter S. , Velcheti Vamsidhar , Freeman Gordon J. , Qi Jun , Miller George , Wong Kwok-Kin
Published: April 2023

Luminex analysis of chemokine/cytokine secretions
Supplementary Table S10 (xlsx) from Circulating Tumor Cells Exhibit Metastatic Tropism and Reveal Brain Metastasis Drivers
Authors: Klotz Remi , Thomas Amal , Teng Teng , Han Sung Min , Iriondo Oihana , Li Lin , Restrepo-Vassalli Sara , Wang Alan , Izadian Negeen , MacKay Matthew , Moon Byoung-San , Liu Kevin J. , Ganesan Sathish Kumar , Lee Grace , Kang Diane S. , Walmsley Charlotte S. , Pinto Christopher , Press Michael F. , Lu Wange , Lu Janice , Juric Dejan , Bardia Aditya , Hicks James , Salhia Bodour , Attenello Frank , Smith Andrew D. , Yu Min
Published: April 2023

List of upregulated genes in CTC-derived brain metastases compare to other metastases (lung, bone and ovary)
Data S1 from Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer
Authors: Kieffer Yann , Hocine Hocine R. , Gentric Géraldine , Pelon Floriane , Bernard Charles , Bourachot Brigitte , Lameiras Sonia , Albergante Luca , Bonneau Claire , Guyard Alice , Tarte Karin , Zinovyev Andrei , Baulande Sylvain , Zalcman Gerard , Vincent-Salomon Anne , Mechta-Grigoriou Fatima
Published: April 2023

Data S1
CD-20-0047R2_Supplementary_Figure_7.pdf from Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade
Authors: Zhang Qu , Luo Jia , Wu Song , Si Han , Gao Chen , Xu Wenjing , Abdullah Shaad E. , Higgs Brandon W. , Dennis Phillip A. , van der Heijden Michiel S. , Segal Neil H. , Chaft Jamie E. , Hembrough Todd , Barrett J. Carl , Hellmann Matthew D.
Published: April 2023

Figure S7
CD-20-0047R2_Supplementary_Figure_1.pdf from Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade
Authors: Zhang Qu , Luo Jia , Wu Song , Si Han , Gao Chen , Xu Wenjing , Abdullah Shaad E. , Higgs Brandon W. , Dennis Phillip A. , van der Heijden Michiel S. , Segal Neil H. , Chaft Jamie E. , Hembrough Todd , Barrett J. Carl , Hellmann Matthew D.
Published: April 2023

Figure S1
CD-20-0047R2_Supplementary_Appendix.docx from Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade
Authors: Zhang Qu , Luo Jia , Wu Song , Si Han , Gao Chen , Xu Wenjing , Abdullah Shaad E. , Higgs Brandon W. , Dennis Phillip A. , van der Heijden Michiel S. , Segal Neil H. , Chaft Jamie E. , Hembrough Todd , Barrett J. Carl , Hellmann Matthew D.
Published: April 2023

Supplementary Materials and Methods
Supplementary Figure S1 from Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer
Authors: Smyth Lillian M. , Piha-Paul Sarina A. , Won Helen H. , Schram Alison M. , Saura Cristina , Loi Sherene , Lu Janice , Shapiro Geoffrey I. , Juric Dejan , Mayer Ingrid A. , Arteaga Carlos L. , de la Fuente Macarena I. , Brufksy Adam M. , Spanggaard Iben , Mau-Sørensen Morten , Arnedos Monica , Moreno Victor , Boni Valentina , Sohn Joohyuk , Schwartzberg Lee S. , Gonzàlez-Farré Xavier , Cervantes Andrés , Bidard François-Clement , Gorelick Alexander N. , Lanman Richard B. , Nagy Rebecca J. , Ulaner Gary A. , Chandarlapaty Sarat , Jhaveri Komal , Gavrila Elena I. , Zimel Catherine , Selcuklu S. Duygu , Melcer Myra , Samoila Aliaksandra , Cai Yanyan , Scaltriti Maurizio , Mann Grace , Xu Feng , Eli Lisa D. , Dujka Melanie , Lalani Alshad S. , Bryce Richard , Baselga José , Taylor Barry S. , Solit David B. , Meric-Bernstam Funda , Hyman David M.
Published: April 2023

PFS of (A) neratinib plus fulvestrant combination cohort and (B) neratinib monotherapy cohort. CI, confidence interval; PFS, progression-free survival.
Supplementary Data from Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis
Authors: Zhang Yaqing , Lazarus Jenny , Steele Nina G. , Yan Wei , Lee Ho-Joon , Nwosu Zeribe C. , Halbrook Christopher J. , Menjivar Rosa E. , Kemp Samantha B. , Sirihorachai Veerin R. , Velez-Delgado Ashley , Donahue Katelyn , Carpenter Eileen S. , Brown Kristee L. , Irizarry-Negron Valerie , Nevison Anna C. , Vinta Alekya , Anderson Michelle A. , Crawford Howard C. , Lyssiotis Costas A. , Frankel Timothy L. , Bednar Filip , Pasca di Magliano Marina
Published: April 2023

Supplemental figure 4 with legend
Supplementary Methods from The TP53 Apoptotic Network Is a Primary Mediator of Resistance to BCL2 Inhibition in AML Cells
Authors: Nechiporuk Tamilla , Kurtz Stephen E. , Nikolova Olga , Liu Tingting , Jones Courtney L. , D'Alessandro Angelo , Culp-Hill Rachel , d'Almeida Amanda , Joshi Sunil K. , Rosenberg Mara , Tognon Cristina E. , Danilov Alexey V. , Druker Brian J. , Chang Bill H. , McWeeney Shannon K , Tyner Jeffrey W.
Published: April 2023

Complete methods
Supplementary Figure 5 from The TP53 Apoptotic Network Is a Primary Mediator of Resistance to BCL2 Inhibition in AML Cells
Authors: Nechiporuk Tamilla , Kurtz Stephen E. , Nikolova Olga , Liu Tingting , Jones Courtney L. , D'Alessandro Angelo , Culp-Hill Rachel , d'Almeida Amanda , Joshi Sunil K. , Rosenberg Mara , Tognon Cristina E. , Danilov Alexey V. , Druker Brian J. , Chang Bill H. , McWeeney Shannon K , Tyner Jeffrey W.
Published: April 2023

Entrectinib arrests cells with loss-of-function alleles for TP53 in G1
Table S5 from Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation
Authors: Gu Zhimin , Liu Yuxuan , Cai Feng , Patrick McKenzie , Zmajkovic Jakub , Cao Hui , Zhang Yuannyu , Tasdogan Alpaslan , Chen Mingyi , Qi Le , Liu Xin , Li Kailong , Lyu Junhua , Dickerson Kathryn E. , Chen Weina , Ni Min , Merritt Matthew E. , Morrison Sean J. , Skoda Radek C. , DeBerardinis Ralph J. , Xu Jian
Published: April 2023

Table S5 shows transitions and parameters used for LC-MS
Table S4 from Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation
Authors: Gu Zhimin , Liu Yuxuan , Cai Feng , Patrick McKenzie , Zmajkovic Jakub , Cao Hui , Zhang Yuannyu , Tasdogan Alpaslan , Chen Mingyi , Qi Le , Liu Xin , Li Kailong , Lyu Junhua , Dickerson Kathryn E. , Chen Weina , Ni Min , Merritt Matthew E. , Morrison Sean J. , Skoda Radek C. , DeBerardinis Ralph J. , Xu Jian
Published: April 2023

Table S4 shows key reagents and resources
Table S6 from The Phenotypes of Proliferating Glioblastoma Cells Reside on a Single Axis of Variation
Authors: Wang Lin , Babikir Husam , Müller Sören , Yagnik Garima , Shamardani Karin , Catalan Francisca , Kohanbash Gary , Alvarado Beatriz , Di Lullo Elizabeth , Kriegstein Arnold , Shah Sumedh , Wadhwa Harsh , Chang Susan M. , Phillips Joanna J. , Aghi Manish K. , Diaz Aaron A.
Published: April 2023

Table S6: Results of the in vitro drug screen.
Supplementary Table 2 from Inactivation of Fbxw7 Impairs dsRNA Sensing and Confers Resistance to PD-1 Blockade
Authors: Gstalder Cécile , Liu David , Miao Diana , Lutterbach Bart , DeVine Alexander L. , Lin Chenyu , Shettigar Megha , Pancholi Priya , Buchbinder Elizabeth I. , Carter Scott L. , Manos Michael P. , Rojas-Rudilla Vanesa , Brennick Ryan , Gjini Evisa , Chen Pei-Hsuan , Lako Ana , Rodig Scott , Yoon Charles H. , Freeman Gordon J. , Barbie David A. , Hodi F. Stephen , Miles Wayne , Van Allen Eliezer M. , Haq Rizwan
Published: April 2023

Comparison of differences in clonal mutations between pre-treatment and resistant tumors
Supplementary Table 1 from Inactivation of Fbxw7 Impairs dsRNA Sensing and Confers Resistance to PD-1 Blockade
Authors: Gstalder Cécile , Liu David , Miao Diana , Lutterbach Bart , DeVine Alexander L. , Lin Chenyu , Shettigar Megha , Pancholi Priya , Buchbinder Elizabeth I. , Carter Scott L. , Manos Michael P. , Rojas-Rudilla Vanesa , Brennick Ryan , Gjini Evisa , Chen Pei-Hsuan , Lako Ana , Rodig Scott , Yoon Charles H. , Freeman Gordon J. , Barbie David A. , Hodi F. Stephen , Miles Wayne , Van Allen Eliezer M. , Haq Rizwan
Published: April 2023

List of all identified somatic mutations in pre-treatment lesion and PD-1 resistant tumors by ABSOLUTE analysis
Figure S13 from Discovery and Features of an Alkylating Signature in Colorectal Cancer
Authors: Gurjao Carino , Zhong Rong , Haruki Koichiro , Li Yvonne Y. , Spurr Liam F. , Lee-Six Henry , Reardon Brendan , Ugai Tomotaka , Zhang Xuehong , Cherniack Andrew D. , Song Mingyang , Van Allen Eliezer M. , Meyerhardt Jeffrey A. , Nowak Jonathan A. , Giovannucci Edward L. , Fuchs Charles S. , Wu Kana , Ogino Shuji , Giannakis Marios
Published: April 2023

Supplemental Figure 13: Distribution of overall red meat intake (A) Overall red meat intake (in grams per day) decile distribution (B) First derivative (per unit rank) of overall red meat intake (in grams per day)
Supplementary Figure 1 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution
Authors: Venkatesan Subramanian , Angelova Mihaela , Puttick Clare , Zhai Haoran , Caswell Deborah R. , Lu Wei-Ting , Dietzen Michelle , Galanos Panagiotis , Evangelou Konstantinos , Bellelli Roberto , Lim Emilia L. , Watkins Thomas B.K. , Rowan Andrew , Teixeira Vitor H. , Zhao Yue , Chen Haiquan , Ngo Bryan , Zalmas Lykourgos-Panagiotis , Al Bakir Maise , Hobor Sebastijan , Grönroos Eva , Pennycuick Adam , Nigro Ersilia , Campbell Brittany B. , Brown William L. , Akarca Ayse U. , Marafioti Teresa , Wu Mary Y. , Howell Michael , Boulton Simon J. , Bertoli Cosetta , Fenton Tim R. , de Bruin Robertus A.M. , Maya-Mendoza Apolinar , Santoni-Rugiu Eric , Hynds Robert E. , Gorgoulis Vassilis G. , Jamal-Hanjani Mariam , McGranahan Nicholas , Harris Reuben S. , Janes Sam M. , Bartkova Jirina , Bakhoum Samuel F. , Bartek Jiri , Kanu Nnennaya , Swanton Charles
Published: April 2023

Assessing APOBEC3 gene expression using immunohistochemical and bioinformatic approaches.
Supplementary Data from CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies
Authors: Wang Dongrui , Prager Briana C. , Gimple Ryan C. , Aguilar Brenda , Alizadeh Darya , Tang Hongzhen , Lv Deguan , Starr Renate , Brito Alfonso , Wu Qiulian , Kim Leo J.Y. , Qiu Zhixin , Lin Peng , Lorenzini Michael H. , Badie Behnam , Forman Stephen J. , Xie Qi , Brown Christine E. , Rich Jeremy N.
Published: April 2023

Supplementary Methods, Figures S1-S14, Table legends, and References
Supplemental Figure 1 from PTHrP Drives Pancreatic Cancer Growth and Metastasis and Reveals a New Therapeutic Vulnerability
Authors: Pitarresi Jason R. , Norgard Robert J. , Chiarella Anna M. , Suzuki Kensuke , Bakir Basil , Sahu Varun , Li Jinyang , Zhao Jun , Marchand Benoît , Wengyn Maximilian D. , Hsieh Antony , Kim Il-Kyu , Zhang Amy , Sellin Karine , Lee Vivian , Takano Shigetsugu , Miyahara Yoji , Ohtsuka Masayuki , Maitra Anirban , Notta Faiyaz , Kremer Richard , Stanger Ben Z. , Rustgi Anil K.
Published: April 2023

Supplemental Figure 1
Supplementary Table from AACR Project GENIE: 100,000 Cases and Beyond
Authors: Pugh Trevor J. , Bell Jonathan L. , Bruce Jeff P. , Doherty Gary J. , Galvin Matthew , Green Michelle F. , Hunter-Zinck Haley , Kumari Priti , Lenoue-Newton Michele L. , Li Marilyn M. , Lindsay James , Mazor Tali , Ovalle Andrea , Sammut Stephen-John , Schultz Nikolaus , Yu Thomas V. , Sweeney Shawn M. , Bernard Brady
Published: April 2023

Supplementary Table from AACR Project GENIE: 100,000 Cases and Beyond
Supplementary Figure from AACR Project GENIE: 100,000 Cases and Beyond
Authors: Pugh Trevor J. , Bell Jonathan L. , Bruce Jeff P. , Doherty Gary J. , Galvin Matthew , Green Michelle F. , Hunter-Zinck Haley , Kumari Priti , Lenoue-Newton Michele L. , Li Marilyn M. , Lindsay James , Mazor Tali , Ovalle Andrea , Sammut Stephen-John , Schultz Nikolaus , Yu Thomas V. , Sweeney Shawn M. , Bernard Brady
Published: April 2023

Supplementary Figure from AACR Project GENIE: 100,000 Cases and Beyond
Supplementary Table from Deconvolving Clinically Relevant Cellular Immune Cross-talk from Bulk Gene Expression Using CODEFACS and LIRICS Stratifies Patients with Melanoma to Anti–PD-1 Therapy
Authors: Wang Kun , Patkar Sushant , Lee Joo Sang , Gertz E. Michael , Robinson Welles , Schischlik Fiorella , Crawford David R. , Schäffer Alejandro A. , Ruppin Eytan
Published: April 2023

Supplementary Table from Deconvolving Clinically Relevant Cellular Immune Cross-talk from Bulk Gene Expression Using CODEFACS and LIRICS Stratifies Patients with Melanoma to Anti–PD-1 Therapy
Supplementary Data from Deconvolving Clinically Relevant Cellular Immune Cross-talk from Bulk Gene Expression Using CODEFACS and LIRICS Stratifies Patients with Melanoma to Anti–PD-1 Therapy
Authors: Wang Kun , Patkar Sushant , Lee Joo Sang , Gertz E. Michael , Robinson Welles , Schischlik Fiorella , Crawford David R. , Schäffer Alejandro A. , Ruppin Eytan
Published: April 2023

Supplementary Data from Deconvolving Clinically Relevant Cellular Immune Cross-talk from Bulk Gene Expression Using CODEFACS and LIRICS Stratifies Patients with Melanoma to Anti–PD-1 Therapy
Supplementary Data from Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations
Authors: Wang Mengzhao , Yang James Chih-Hsin , Mitchell Paul L. , Fang Jian , Camidge D. Ross , Nian Weiqi , Chiu Chao-Hua , Zhou Jianying , Zhao Yanqiu , Su Wu-Chou , Yang Tsung-Ying , Zhu Viola W. , Millward Michael , Fan Yun , Huang Wen-Tsung , Cheng Ying , Jiang Liyan , Brungs Daniel , Bazhenova Lyudmila , Lee Chee Khoon , Gao Bo , Xu Yan , Hsu Wei-Hsun , Zheng Li , Jänne Pasi A.
Published: April 2023

Supplementary Data from Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations
Supplementary Table from Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
Authors: Chang Chewei Anderson , Jen Jayu , Jiang Shaowen , Sayad Azin , Mer Arvind Singh , Brown Kevin R. , Nixon Allison M.L. , Dhabaria Avantika , Tang Kwan Ho , Venet David , Sotiriou Christos , Deng Jiehui , Wong Kwok-kin , Adams Sylvia , Meyn Peter , Heguy Adriana , Skok Jane A. , Tsirigos Aristotelis , Ueberheide Beatrix , Moffat Jason , Singh Abhyudai , Haibe-Kains Benjamin , Khodadadi-Jamayran Alireza , Neel Benjamin G.
Published: April 2023

Supplementary Table from Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
Supplementary Table from Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma
Authors: Song Xiaofei , Chang Shiun , Seminario-Vidal Lucia , de Mingo Pulido Alvaro , Tordesillas Leticia , Song Xingzhi , Reed Rhianna A. , Harkins Andrea , Whiddon Shannen , Nguyen Jonathan V. , Segura Carlos Moran , Zhang Chaomei , Yoder Sean , Sayegh Zena , Zhao Yun , Messina Jane L. , Harro Carly M. , Zhang Xiaohui , Conejo-Garcia José R. , Berglund Anders , Sokol Lubomir , Zhang Jianhua , Rodriguez Paulo C. , Mulé James J. , Futreal Andrew P. , Tsai Kenneth Y. , Chen Pei-Ling
Published: April 2023

Supplementary Table from Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma
Supplementary Data from Synthetic Essentiality of Tryptophan 2,3-Dioxygenase 2 in APC-Mutated Colorectal Cancer
Authors: Lee Rumi , Li Jiexi , Li Jun , Wu Chang-Jiun , Jiang Shan , Hsu Wen-Hao , Chakravarti Deepavali , Chen Peiwen , LaBella Kyle A. , Li Jing , Spring Denise J. , Zhao Di , Wang Y. Alan , DePinho Ronald A.
Published: April 2023

Supplementary Data from Synthetic Essentiality of Tryptophan 2,3-Dioxygenase 2 in APC-Mutated Colorectal Cancer
Supplementary Table from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer
Authors: Schalck Aislyn , Sakellariou-Thompson Donastas , Forget Marie-Andrée , Sei Emi , Hughes Tara G. , Reuben Alexandre , Bai Shanshan , Hu Min , Kumar Tapsi , Hurd Mark W. , Katz Matthew H.G. , Tzeng Ching-Wei D. , Pant Shubham , Javle Milind , Fogelman David R. , Maitra Anirban , Haymaker Cara L. , Kim Michael P. , Navin Nicholas E. , Bernatchez Chantale
Published: April 2023

Supplementary Table from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer
Supplementary Figure from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer
Authors: Schalck Aislyn , Sakellariou-Thompson Donastas , Forget Marie-Andrée , Sei Emi , Hughes Tara G. , Reuben Alexandre , Bai Shanshan , Hu Min , Kumar Tapsi , Hurd Mark W. , Katz Matthew H.G. , Tzeng Ching-Wei D. , Pant Shubham , Javle Milind , Fogelman David R. , Maitra Anirban , Haymaker Cara L. , Kim Michael P. , Navin Nicholas E. , Bernatchez Chantale
Published: April 2023

Supplementary Figure from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer
Data from Functional Characterization of an Isoform-Selective Inhibitor of PI3K-p110β as a Potential Anticancer Agent
Authors: Ni Jing , Liu Qingsong , Xie Shaozhen , Carlson Coby , Von Thanh , Vogel Kurt , Riddle Steve , Benes Cyril , Eck Michael , Roberts Thomas , Gray Nathanael , Zhao Jean
Published: April 2023

Abstract
Genetic approaches have shown that the p110β isoform of class Ia phosphatidylinositol-3-kinase (PI3K) is essential for the growth of PTEN-null tumors. Thus, it is desirable to develop p110β-specific inhibitors for cancer therapy. Using a panel of PI3K isoform-specific cellular assays, we screened a collection of compounds possessing activities against kinases in the PI3K superfamily and identified a potent and selective p110β inhibitor: KIN-193. We show that KIN-193 is efficacious specifically in blocking AKT signaling and tumor growth that are dependent on p110β activation or PTEN loss. Broad profiling across a panel of 422 human tumor cell lines shows that the PTEN mutation status of cancer cells strongly correlates with their response to KIN-193. Together, our data provide the first pharmacologic evidence that PTEN-deficient tumors are dependent on p110β in animals and suggest that KIN-193 can be pursued as a drug to treat tumors that are dependent on p110β while sparing other PI3K isoforms.

Significance: We report the first functional characterization of a p110β-selective inhibitor, KIN-193, that is efficacious as an antitumor agent in mice. We show that this class of inhibitor holds great promise as a pharmacologic agent that could be used to address the potential therapeutic benefit of treating p110β-dependent PTEN-deficient human tumors. Cancer Discov; 2(5); 425–33. ©2012 AACR.

Read the Commentary on this article by Shepherd and Denny, p. 393.

This article is highlighted in the In This Issue feature, p. 377.
Data from Proteomic Profiling Identifies Dysregulated Pathways in Small Cell Lung Cancer and Novel Therapeutic Targets Including PARP1
Authors: Byers Lauren Averett , Wang Jing , Nilsson Monique B. , Fujimoto Junya , Saintigny Pierre , Yordy John , Giri Uma , Peyton Michael , Fan You Hong , Diao Lixia , Masrorpour Fatemeh , Shen Li , Liu Wenbin , Duchemann Boris , Tumula Praveen , Bhardwaj Vikas , Welsh James , Weber Stephanie , Glisson Bonnie S. , Kalhor Neda , Wistuba Ignacio I. , Girard Luc , Lippman Scott M. , Mills Gordon B. , Coombes Kevin R. , Weinstein John N. , Minna John D. , Heymach John V.
Published: April 2023

Abstract
Small cell lung cancer (SCLC) is an aggressive malignancy distinct from non–small cell lung cancer (NSCLC) in its metastatic potential and treatment response. Using an integrative proteomic and transcriptomic analysis, we investigated molecular differences contributing to the distinct clinical behavior of SCLCs and NSCLCs. SCLCs showed lower levels of several receptor tyrosine kinases and decreased activation of phosphoinositide 3-kinase (PI3K) and Ras/mitogen-activated protein (MAP)/extracellular signal–regulated kinase (ERK) kinase (MEK) pathways but significantly increased levels of E2F1-regulated factors including enhancer of zeste homolog 2 (EZH2), thymidylate synthase, apoptosis mediators, and DNA repair proteins. In addition, PARP1, a DNA repair protein and E2F1 co-activator, was highly expressed at the mRNA and protein levels in SCLCs. SCLC growth was inhibited by PARP1 and EZH2 knockdown. Furthermore, SCLC was significantly more sensitive to PARP inhibitors than were NSCLCs, and PARP inhibition downregulated key components of the DNA repair machinery and enhanced the efficacy of chemotherapy.

Significance: SCLC is a highly lethal cancer with a 5-year survival rate of less than 10%. To date, no molecularly targeted agents have prolonged survival in patients with SCLCs. As a step toward identifying new targets, we systematically profiled SCLCs with a focus on therapeutically relevant signaling pathways. Our data reveal fundamental differences in the patterns of pathway activation in SCLCs and NSCLCs and identify several potential therapeutic targets for SCLCs, including PARP1 and EZH2. On the basis of these results, clinical studies evaluating PARP and EZH2 inhibition, together with chemotherapy or other agents, warrant further investigation. Cancer Discov; 2(9); 798–811. ©2012 AACR.

Read the Commentary on this article by Rosell and Wannesson, p. 769.

This article is highlighted in the In This Issue feature, p. 753.
Data from Genomic Landscape of Ewing Sarcoma Defines an Aggressive Subtype with Co-Association of STAG2 and TP53 Mutations
Authors: Tirode Franck , Surdez Didier , Ma Xiaotu , Parker Matthew , Le Deley Marie Cécile , Bahrami Armita , Zhang Zhaojie , Lapouble Eve , Grossetête-Lalami Sandrine , Rusch Michael , Reynaud Stéphanie , Rio-Frio Thomas , Hedlund Erin , Wu Gang , Chen Xiang , Pierron Gaelle , Oberlin Odile , Zaidi Sakina , Lemmon Gordon , Gupta Pankaj , Vadodaria Bhavin , Easton John , Gut Marta , Ding Li , Mardis Elaine R. , Wilson Richard K. , Shurtleff Sheila , Laurence Valérie , Michon Jean , Marec-Bérard Perrine , Gut Ivo , Downing James , Dyer Michael , Zhang Jinghui , Delattre Olivier
Published: April 2023

Abstract
Ewing sarcoma is a primary bone tumor initiated by EWSR1–ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants, and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2-immunonegative cells in relapsed tumors as compared with matched diagnostic samples.

Significance: Whole-genome sequencing reveals that the somatic mutation rate in Ewing sarcoma is low. Tumors that harbor STAG2 and TP53 mutations have a particularly dismal prognosis with current treatments and require alternative therapies. Novel drugs that target epigenetic regulators may constitute viable therapeutic strategies in a subset of patients with mutations in chromatin modifiers. Cancer Discov; 4(11); 1342–53. ©2014 AACR.

This article is highlighted in the In This Issue feature, p. 1243
Data from Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers
Authors: Pickering Curtis R. , Zhang Jiexin , Yoo Suk Young , Bengtsson Linnea , Moorthy Shhyam , Neskey David M. , Zhao Mei , Ortega Alves Marcus V. , Chang Kyle , Drummond Jennifer , Cortez Elsa , Xie Tong-xin , Zhang Di , Chung Woonbok , Issa Jean-Pierre J. , Zweidler-McKay Patrick A. , Wu Xifeng , El-Naggar Adel K. , Weinstein John N. , Wang Jing , Muzny Donna M. , Gibbs Richard A. , Wheeler David A. , Myers Jeffrey N. , Frederick Mitchell J.
Published: April 2023

Abstract
The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating subset of head and neck cancers.

Significance: This is the first integrated genomic analysis of OSCC. Only through integrated multiplatform analysis was it possible to identify four key pathways. We also discovered a new disease subtype associated with CASP8 and HRAS mutation. Finally, many candidate targetable events were found and provide hope for future genomically driven therapeutic strategies. Cancer Discov; 3(7); 770–81. ©2013 AACR.

See related commentary by Iglesias-Bartolome et al., p. 722

This article is highlighted in the In This Issue feature, p. 705
Data from Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib
Authors: Wagle Nikhil , Grabiner Brian C. , Van Allen Eliezer M. , Hodis Eran , Jacobus Susanna , Supko Jeffrey G. , Stewart Michelle , Choueiri Toni K. , Gandhi Leena , Cleary James M. , Elfiky Aymen A. , Taplin Mary Ellen , Stack Edward C. , Signoretti Sabina , Loda Massimo , Shapiro Geoffrey I. , Sabatini David M. , Lander Eric S. , Gabriel Stacey B. , Kantoff Philip W. , Garraway Levi A. , Rosenberg Jonathan E.
Published: April 2023

Abstract
Understanding the genetic mechanisms of sensitivity to targeted anticancer therapies may improve patient selection, response to therapy, and rational treatment designs. One approach to increase this understanding involves detailed studies of exceptional responders: rare patients with unexpected exquisite sensitivity or durable responses to therapy. We identified an exceptional responder in a phase I study of pazopanib and everolimus in advanced solid tumors. Whole-exome sequencing of a patient with a 14-month complete response on this trial revealed two concurrent mutations in mTOR, the target of everolimus. In vitro experiments demonstrate that both mutations are activating, suggesting a biologic mechanism for exquisite sensitivity to everolimus in this patient. The use of precision (or “personalized”) medicine approaches to screen patients with cancer for alterations in the mTOR pathway may help to identify subsets of patients who may benefit from targeted therapies directed against mTOR.

Significance: The study of exceptional responders represents a promising approach to better understanding the mechanisms that underlie sensitivity to targeted anticancer therapies. Here, we identify two activating mTOR mutations in a patient with exquisite sensitivity to everolimus and pazopanib, suggesting an approach to identifying patients who might benefit most from mTOR inhibitors. Cancer Discov; 4(5); 546–53. ©2014 AACR.

See related commentary by Rejto and Abraham, p. 513

This article is highlighted in the In This Issue feature, p. 495
Data from Autophagy Sustains Pancreatic Cancer Growth through Both Cell-Autonomous and Nonautonomous Mechanisms
Authors: Yang Annan , Herter-Sprie Grit , Zhang Haikuo , Lin Elaine Y. , Biancur Douglas , Wang Xiaoxu , Deng Jiehui , Hai Josephine , Yang Shenghong , Wong Kwok-Kin , Kimmelman Alec C.
Published: April 2023

Abstract
Autophagy has been shown to be elevated in pancreatic ductal adenocarcinoma (PDAC), and its role in promoting established tumor growth has made it a promising therapeutic target. However, due to limitations of prior mouse models as well as the lack of potent and selective autophagy inhibitors, the ability to fully assess the mechanistic basis of how autophagy supports pancreatic cancer has been limited. To test the feasibility of treating PDAC using autophagy inhibition and further our understanding of the mechanisms of protumor effects of autophagy, we developed a mouse model that allowed the acute and reversible inhibition of autophagy. We observed that autophagy inhibition causes significant tumor regression in an autochthonous mouse model of PDAC. A detailed analysis of these effects indicated that the tumor regression was likely multifactorial, involving both tumor cell–intrinsic and host effects. Thus, our study supports that autophagy inhibition in PDAC may have future utility in the treatment of pancreatic cancer and illustrates the importance of assessing complex biological processes in relevant autochthonous models.

Significance: This work demonstrates that autophagy is critical pancreatic tumor maintenance through tumor cell–intrinsic and –extrinsic mechanisms. These results have direct clinical relevance to ongoing clinical trials as well as drug-development initiatives. Cancer Discov; 8(3); 276–87. ©2018 AACR.

See related commentary by Noguera-Ortega and Amaravadi, p. 266.

This article is highlighted in the In This Issue feature, p. 253
Data from Homophilic CD44 Interactions Mediate Tumor Cell Aggregation and Polyclonal Metastasis in Patient-Derived Breast Cancer Models
Authors: Liu Xia , Taftaf Rokana , Kawaguchi Madoka , Chang Ya-Fang , Chen Wenjing , Entenberg David , Zhang Youbin , Gerratana Lorenzo , Huang Simo , Patel Dhwani B. , Tsui Elizabeth , Adorno-Cruz Valery , Chirieleison Steven M. , Cao Yue , Harney Allison S. , Patel Shivani , Patsialou Antonia , Shen Yang , Avril Stefanie , Gilmore Hannah L. , Lathia Justin D. , Abbott Derek W. , Cristofanilli Massimo , Condeelis John S. , Liu Huiping
Published: April 2023

Abstract
Circulating tumor cells (CTC) seed cancer metastases; however, the underlying cellular and molecular mechanisms remain unclear. CTC clusters were less frequently detected but more metastatic than single CTCs of patients with triple-negative breast cancer and representative patient-derived xenograft models. Using intravital multiphoton microscopic imaging, we found that clustered tumor cells in migration and circulation resulted from aggregation of individual tumor cells rather than collective migration and cohesive shedding. Aggregated tumor cells exhibited enriched expression of the breast cancer stem cell marker CD44 and promoted tumorigenesis and polyclonal metastasis. Depletion of CD44 effectively prevented tumor cell aggregation and decreased PAK2 levels. The intercellular CD44–CD44 homophilic interactions directed multicellular aggregation, requiring its N-terminal domain, and initiated CD44–PAK2 interactions for further activation of FAK signaling. Our studies highlight that CD44+ CTC clusters, whose presence is correlated with a poor prognosis of patients with breast cancer, can serve as novel therapeutic targets of polyclonal metastasis.
Significance:
CTCs not only serve as important biomarkers for liquid biopsies, but also mediate devastating metastases. CD44 homophilic interactions and subsequent CD44–PAK2 interactions mediate tumor cluster aggregation. This will lead to innovative biomarker applications to predict prognosis, facilitate development of new targeting strategies to block polyclonal metastasis, and improve clinical outcomes.

See related commentary by Rodrigues and Vanharanta, p. 22.

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