bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Table S2 from In Vitro and In Vivo Synergistic Antitumor Activity of the Combination of BKM120 and Erlotinib in Head and Neck Cancer: Mechanism of Apoptosis and Resistance
Authors: Anisuzzaman Abu Syed Md , Haque Abedul , Wang Dongsheng , Rahman Mohammad Aminur , Zhang Chao , Chen Zhengjia , Chen Zhuo Georgia , Shin Dong M. , Amin A.R.M. Ruhul
Published: April 2023

Table S2: Source and dilution factors of antibodies used
Figure S4 from Arsenic Trioxide and Sorafenib Induce Synthetic Lethality of FLT3-ITD Acute Myeloid Leukemia Cells
Authors: Wang Rui , Li Ying , Gong Ping , Gabrilove Janice , Waxman Samuel , Jing Yongkui
Published: April 2023

The effect of Sorafenib and AC220 on the levels of GSH.
Figure S3 from Arsenic Trioxide and Sorafenib Induce Synthetic Lethality of FLT3-ITD Acute Myeloid Leukemia Cells
Authors: Wang Rui , Li Ying , Gong Ping , Gabrilove Janice , Waxman Samuel , Jing Yongkui
Published: April 2023

The effect of SB216763 on the apoptosis induction of ATO with Sorafenib.
Supplementary Figure S3 from Highly Potent, Anthracycline-based Antibody–Drug Conjugates Generated by Enzymatic, Site-specific Conjugation
Authors: Stefan Nikolas , Gébleux Rémy , Waldmeier Lorenz , Hell Tamara , Escher Marie , Wolter Fabian I. , Grawunder Ulf , Beerli Roger R.
Published: April 2023

Quantification of HER2 expression levels on T47D and SKBR3 breast cancer cells.
Supplementary Figure Legends from Highly Potent, Anthracycline-based Antibody–Drug Conjugates Generated by Enzymatic, Site-specific Conjugation
Authors: Stefan Nikolas , Gébleux Rémy , Waldmeier Lorenz , Hell Tamara , Escher Marie , Wolter Fabian I. , Grawunder Ulf , Beerli Roger R.
Published: April 2023

Legends to Supplementary Figures S1-S6
Supplementary Table S1 from Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells
Authors: Koo Chuay-Yeng , Giacomini Caterina , Reyes-Corral Marta , Olmos Yolanda , Tavares Ignatius A. , Marson Charles M. , Linardopoulos Spiros , Tutt Andrew N. , Morris Jonathan D.H.
Published: April 2023

Profile showing the activity of 70 different kinases in the presence of TAOK inhibitor compounds. In vitro kinase assays were carried out incubating kinases with or without compound 43 or 63 (0.3 µM) as indicated. Changes in the phosphorylation of MBP and activity of each enzyme are shown as percentages relative to control samples (n = 2).
Supplementary Movie S2 from Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells
Authors: Koo Chuay-Yeng , Giacomini Caterina , Reyes-Corral Marta , Olmos Yolanda , Tavares Ignatius A. , Marson Charles M. , Linardopoulos Spiros , Tutt Andrew N. , Morris Jonathan D.H.
Published: April 2023

Live images of growing MCF-10A cells treated with compound 43. Representative time-lapse video images showing GFP-α-tubulin expressing MCF10-A cells incubated in growth medium containing compound 43 (5 µM) for 48 hours.
Supplementary Movie S1 from Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells
Authors: Koo Chuay-Yeng , Giacomini Caterina , Reyes-Corral Marta , Olmos Yolanda , Tavares Ignatius A. , Marson Charles M. , Linardopoulos Spiros , Tutt Andrew N. , Morris Jonathan D.H.
Published: April 2023

Live images of growing MCF-10A cells. Representative time-lapse video images showing GFP-α-tubulin expressing MCF10-A cells incubated in growth medium containing equivalent DMSO (0.05%) for 48 hours.
Supplementary Materials, Methods and Legends from Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells
Authors: Koo Chuay-Yeng , Giacomini Caterina , Reyes-Corral Marta , Olmos Yolanda , Tavares Ignatius A. , Marson Charles M. , Linardopoulos Spiros , Tutt Andrew N. , Morris Jonathan D.H.
Published: April 2023

Supplementary Materials, Methods and Legends
supplementary methods from Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation
Authors: Simmons John K. , Michalowski Aleksandra M. , Gamache Benjamin J. , DuBois Wendy , Patel Jyoti , Zhang Ke , Gary Joy , Zhang Shuling , Gaikwad Snehal , Connors Daniel , Watson Nicholas , Leon Elena , Chen Jin-Qiu , Kuehl W. Michael , Lee Maxwell P. , Zingone Adriana , Landgren Ola , Ordentlich Peter , Huang Jing , Mock Beverly A.
Published: April 2023

supplementary statistical methods and primer sequences
Supplemental Figure 1 from Interleukin-24 (IL24) Is Suppressed by PAX3-FOXO1 and Is a Novel Therapy for Rhabdomyosarcoma
Authors: Lacey Alexandra , Hedrick Erik , Cheng Yating , Mohankumar Kumaravel , Warren Melanie , Safe Stephen
Published: April 2023

(A) IPA analysis of pathways observed after knockdown of PAX3-FOXO1 in Rh30 cells. (B.) Knockdown of NR4A1 in ARMS cells by a second oligonucleotide targeting NR4A1.
Suporting Video Legends from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Authors: Indorato Rose-Laure , Talapatra Sandeep K. , Lin Fangzhu , Haider Shozeb , Mackay Simon P. , Kozielski Frank , Skoufias Dimitrios A.
Published: April 2023

SV1-SV6: Time lapse imaging of untreated, Arry-520 and ispinesib treated naive U2OS cells, Eg5(D130) and Eg5(L214) expressing U2OS cells followed for 16h. SV7-SV12: Molecular dynamics simulations of either Eg5(WT), or Eg5(D130) or Eg5(L214) motor domain bound to either Arry-520 or ispinesib.
Supplementary Figures from Acquired Resistance to the Hsp90 Inhibitor, Ganetespib, in KRAS-Mutant NSCLC Is Mediated via Reactivation of the ERK–p90RSK–mTOR Signaling Network
Authors: Chatterjee Suman , Huang Eric H.-B. , Christie Ian , Kurland Brenda F. , Burns Timothy F.
Published: April 2023

Six Figures
Supplement 1. sgRNA sequences targeting PSMC1 to C6 from CRISPR Genome-Wide Screening Identifies Dependence on the Proteasome Subunit PSMC6 for Bortezomib Sensitivity in Multiple Myeloma
Authors: Shi Chang-Xin , Kortüm K. Martin , Zhu Yuan Xiao , Bruins Laura A. , Jedlowski Patrick , Votruba Patrick G. , Luo Moulun , Stewart Robert A. , Ahmann Jonathan , Braggio Esteban , Stewart A. Keith
Published: April 2023

sgRNA sequences targeting PSMC1 to C6
Supplementary legends from β-Catenin mRNA Silencing and MEK Inhibition Display Synergistic Efficacy in Preclinical Tumor Models
Authors: Ganesh Shanthi , Shui Xue , Craig Kevin P. , Koser Martin L. , Chopda Girish R. , Cyr Wendy A. , Lai Chengjung , Dudek Henryk , Wang Weimin , Brown Bob D. , Abrams Marc T.
Published: April 2023

Legends for supplementary figures
Figure S1 from Cyclooxygenase-2 Influences Response to Cotargeting of MEK and CDK4/6 in a Subpopulation of Pancreatic Cancers
Authors: Maust Joel D. , Frankowski-McGregor Christy L. , Bankhead Armand , Simeone Diane M. , Sebolt-Leopold Judith S.
Published: April 2023

Impact of drug concentration and kinase inhibitor selection on synergistic response (L3.6pl model)
Supplementary Figures S1-S2 from The Exportin-1 Inhibitor Selinexor Exerts Superior Antitumor Activity when Combined with T-Cell Checkpoint Inhibitors
Authors: Farren Matthew R. , Hennessey Rebecca C. , Shakya Reena , Elnaggar Omar , Young Gregory , Kendra Kari , Landesman Yosef , Elloul Sivan , Crochiere Marsha , Klebanov Boris , Kashyap Trinayan , Burd Christin E. , Lesinski Gregory B.
Published: April 2023

Supplemental Figure S1: Effects of alternative dosing schedules for selinexor (15 mg/kg) and anti-PD-1 on systemic immune populations; Supplemental Figure S2: Effects of alternative dosing schedules for selinexor (10 mg/kg) and anti-PD-1 on systemic immune populations.
Supplementary Figure S3 from Functional Analysis of Somatic Mutations Affecting Receptor Tyrosine Kinase Family in Metastatic Colorectal Cancer
Authors: Duplaquet Leslie , Figeac Martin , Leprêtre Frédéric , Frandemiche Charline , Villenet Céline , Sebda Shéhérazade , Sarafan-Vasseur Nasrin , Bénozène Mélanie , Vinchent Audrey , Goormachtigh Gautier , Wicquart Laurence , Rousseau Nathalie , Beaussire Ludivine , Truant Stéphanie , Michel Pierre , Sabourin Jean-Christophe , Galateau-Sallé Françoise , Copin Marie-Christine , Zalcman Gérard , De Launoit Yvan , Fafeur Véronique , Tulasne David
Published: April 2023

Supplementary Figure S3: Expression vector, mutagenesis oligonucleotides, and antibodies used for the functional analysis of the 8 somatic mutations in RTKs
Figure S5 from A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival
Authors: Mohanty Suchismita , Chen Zixin , Li Kai , Morais Goreti Ribeiro , Klockow Jessica , Yerneni Ketan , Pisani Laura , Chin Frederick T. , Mitra Siddharta , Cheshier Samuel , Chang Edwin , Gambhir Sanjiv Sam , Rao Jianghong , Loadman Paul M. , Falconer Robert A. , Daldrup-Link Heike E.
Published: April 2023

Effect of CLIO-ICT on mouse body weight
Supplementary Figure S3 from Sentinel Lymph Node–Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model
Authors: Tanaka Yuya , Araki Koji , Tanaka Shingo , Miyagawa Yoshihiro , Suzuki Hiroshi , Kamide Daisuke , Tomifuji Masayuki , Uno Kosuke , Kimura Eiko , Yamashita Taku , Ueda Yasuji , Shiotani Akihiro
Published: April 2023

uPA activity assay for various types of squamous cell carcinoma cell lines.
Figure S4 from The Rolipram–Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway
Authors: Cho Hee-Yeon , Thein Thu Zan , Wang Weijun , Swenson Stephen D. , Fayngor Rochelle A. , Ou Mengting , Marín-Ramos Nagore I. , Schönthal Axel H. , Hofman Florence M. , Chen Thomas C.
Published: April 2023

Blood cell counts following 20 days of NEO214 treatment.
Supplementary Figure S7 from Preclinical Investigation of 212Pb-DOTAMTATE for Peptide Receptor Radionuclide Therapy in a Neuroendocrine Tumor Model
Authors: Stallons Tania A. Rozgaja , Saidi Amal , Tworowska Izabela , Delpassand Ebrahim S. , Torgue Julien J.
Published: April 2023

A biodistribution study was done in CD-1 non-tumor bearing mice to compare the uptake of 212Pb-DOTAMTATE and 203Pb-DOTAMTATE at 4hr and 24hr post drug injection. No significant difference is observed between the 212Pb-DOTAMTATE and 203Pb-DOTAMTATE in all critical organs at either of the two timepoints.
Supplementary Figure S3 from Preclinical Investigation of 212Pb-DOTAMTATE for Peptide Receptor Radionuclide Therapy in a Neuroendocrine Tumor Model
Authors: Stallons Tania A. Rozgaja , Saidi Amal , Tworowska Izabela , Delpassand Ebrahim S. , Torgue Julien J.
Published: April 2023

A biodistribution study in athymic nude tumor bearing mice four hours post drug injection showed similar tumor uptake in tumors between 250mm3 and 1500mm3 (Panel A). Results were similar in all other organs examined by biodistribution. Examination of individual tumors within each group showed no correlation between tumor volume and drug uptake in tumors <500mm3 up to 1500mm3 (Panel B).
Supplementary Table S1 from Glibenclamide Targets Sulfonylurea Receptor 1 to Inhibit p70S6K Activity and Upregulate KLF4 Expression to Suppress Non-Small Cell Lung Carcinoma
Authors: Xu Kexin , Sun Geng , Li Min , Chen Hongling , Zhang Zuhao , Qian Xixi , Li Ping , Xu Lin , Huang Wenbin , Wang Xuerong
Published: April 2023

Supplementary Table S1 shows the clinicopathological characteristics of non-small cell lung carcinoma patients in Fig. 1C.
Supplementary Figure S8 from Glibenclamide Targets Sulfonylurea Receptor 1 to Inhibit p70S6K Activity and Upregulate KLF4 Expression to Suppress Non-Small Cell Lung Carcinoma
Authors: Xu Kexin , Sun Geng , Li Min , Chen Hongling , Zhang Zuhao , Qian Xixi , Li Ping , Xu Lin , Huang Wenbin , Wang Xuerong
Published: April 2023

Supplementary Figure S8 shows photos and histological sections of xenografts and livers.
Supplementary Data from The Neddylation Inhibitor Pevonedistat (MLN4924) Suppresses and Radiosensitizes Head and Neck Squamous Carcinoma Cells and Tumors
Authors: Vanderdys Vanessa , Allak Amir , Guessous Fadila , Benamar Mouadh , Read Paul W. , Jameson Mark J. , Abbas Tarek
Published: April 2023

Supplemental Figure 1: CDT2 is overexpressed in HNSCCs;Supplemental Figure 2: Elevated CDT2 expression in HNSCC dose not correlate with overall disease survival;Supplemental Figure 3: Treatment of HNSCC cells with pevonedistat causes transient increases in the steady-state level of CRL4CDT2 substrates;Supplemental Figure 4: Transient exposure of Cal27 HNSCC cells to pevonedistat induces permanent growth inhibition;Supplemental Figure 5: Pevonedistat radiosensitizes HPV-ve HNSCC cells;Supplemental Figure 6: Ionizing radiation stimulates pevonedistat-induced rereplication in HPVve HNSCC cells.
Supplemental Table 3 from Nanoparticle-Based Celecoxib and Plumbagin for the Synergistic Treatment of Melanoma
Authors: Gowda Raghavendra , Kardos Gregory , Sharma Arati , Singh Sanjay , Robertson Gavin P.
Published: April 2023

Supplemental Table 3. CelePlum-777 did not act through AKT or cPLA2 signaling.
Supplemental Legends from Nanoparticle-Based Celecoxib and Plumbagin for the Synergistic Treatment of Melanoma
Authors: Gowda Raghavendra , Kardos Gregory , Sharma Arati , Singh Sanjay , Robertson Gavin P.
Published: April 2023

Supplemental Legends
Supplemental Figure 2 from Nanoparticle-Based Celecoxib and Plumbagin for the Synergistic Treatment of Melanoma
Authors: Gowda Raghavendra , Kardos Gregory , Sharma Arati , Singh Sanjay , Robertson Gavin P.
Published: April 2023

Supplemental Figure 2. Thermal stability of Celecoxib and Plumbagin.
Supplementary Table S1 from Radiation Responses of 2D and 3D Glioblastoma Cells: A Novel, 3D-specific Radioprotective Role of VEGF/Akt Signaling through Functional Activation of NHEJ
Authors: Gomez-Roman Natividad , Chong Ming Y , Chahal Sandeep K. , Caragher Seamus P. , Jackson Mark R. , Stevenson Katrina H. , Dongre Sidhartha A. , Chalmers Anthony J.
Published: April 2023

Reagents
Supplementary Figure S5 from Radiation Responses of 2D and 3D Glioblastoma Cells: A Novel, 3D-specific Radioprotective Role of VEGF/Akt Signaling through Functional Activation of NHEJ
Authors: Gomez-Roman Natividad , Chong Ming Y , Chahal Sandeep K. , Caragher Seamus P. , Jackson Mark R. , Stevenson Katrina H. , Dongre Sidhartha A. , Chalmers Anthony J.
Published: April 2023

Erlotinib radiosensitisation of 2D GSC is VEGF-independent. A-D, Clonogenic survival of R10 GSC grown in 3D (A) and 2D (B-D) conditions and irradiated with single doses of X-rays (0-6 Gy; n=3) 2 hours after treatment of erlotinib (1microM) or vehicle (DMSO) in the presence (+VEGF) or absence (-VEGF) of VEGF (3 ng/ml). Mean {plus minus} SD of 3 independent experiments is shown; curves are fitted to a linear quadratic model. Erlotinib significantly radioprotected 3D VEGF-deprived cells (two-way ANOVA; R10 3D (-) VEGF vehicle vs 3D (-) VEGF plus erlotinib p < 0.05). No significant effect of erlotinib was observed in the presence of VEGF in 3D cells. Erlotinib radiosensitised 2D G7, E2 and R10 cells irrespective of VEGF presence (B-D). E, Quantification of gH2AX foci per nucleus in G7 3D cells treated with erlotinib in the absence of VEGF, or with VEGF after radiation treatment (24 h). Graph represents mean of medians from 3 independent experiments. p values calculated by t test (* p<0.01; ** p<0.001). F and G, Quantification of pDNA-PKcs (upper graph) and Rad51 foci (lower graph) per nucleus following radiation treatment. Graph represents mean of medians from 3 independent experiments. p values calculated by t test (* p <0.01; ** p <0.001).H, Quantification of DNA-PKcs and EGFR colocalisation per nucleus in E2 3D GSC. Approximately 40 nuclei were quantified for each condition. Box and whisker plots represent median number of signal per nucleus, p values calculated by Mann Whitney U test (*p<0.05; **p<0.005).
Supplementary Figure S3 from Radiation Responses of 2D and 3D Glioblastoma Cells: A Novel, 3D-specific Radioprotective Role of VEGF/Akt Signaling through Functional Activation of NHEJ
Authors: Gomez-Roman Natividad , Chong Ming Y , Chahal Sandeep K. , Caragher Seamus P. , Jackson Mark R. , Stevenson Katrina H. , Dongre Sidhartha A. , Chalmers Anthony J.
Published: April 2023

2D and 3D GSC exhibit similar levels of CENPF positive cells and radiation response to MK-2206. A, Representative immunofluorescent images of G7 and E2 cells grown in 2D or 3D conditions for CENPF. B, Percentage of cells showing CENPF staining per field as in (A). Graph depicts mean {plus minus}SD of three independent experiments. C, Representative immunofluorescent images for gammaH2AX foci of E2 GSC grown in 2D conditions fixed with 2% PFA at the indicated time points following ionising radiation (5 Gy). D, Percentages of cells displaying micronuclei. An average of 350 cells/condition/experiment were identified randomly and scored. Mean {plus minus} SEM of 3 independent experiments. P values calculated by t test. Aberrant DNA damage repair in VEGF-deprived GSC. E, Quantification of pDNA-PKcs (Thr2609) foci per nucleus following radiation treatment. Graph represents mean of medians from 3 independent experiments. p values calculated by t test (* p<0.01; ** p<0.001). F, Representative immunofluorescent images of G7 GSC grown in 3D conditions for BRCA2 foci at 3 hours following ionising radiation (5 Gy) in the presence or absence of VEGF. G, Percentage of nuclei exhibiting Rad51 foci. Positive Rad51 nuclei (>3 Rad51 foci per nucleus) were quantified and expressed as the percentage of total cells per image field. 3 fields (~ 30-50 cells per field) from 4 independent experiments were quantified. Graph depicts mean {plus minus}SD.
Supplementary Figure 6 from Precision Chemoradiotherapy for HER2 Tumors Using Antibody Conjugates of an Auristatin Derivative with Reduced Cell Permeability
Authors: Hingorani Dina V. , Doan Matthew K. , Camargo Maria F. , Aguilera Joseph , Song Seung M. , Pizzo Donald , Scanderbeg Daniel J. , Cohen Ezra E.W. , Lowy Andrew M. , Adams Stephen R. , Advani Sunil J.
Published: April 2023

Pertuzumab conjugated MMAE and IR tumor control.
Supplementary Figure 3 from Precision Chemoradiotherapy for HER2 Tumors Using Antibody Conjugates of an Auristatin Derivative with Reduced Cell Permeability
Authors: Hingorani Dina V. , Doan Matthew K. , Camargo Maria F. , Aguilera Joseph , Song Seung M. , Pizzo Donald , Scanderbeg Daniel J. , Cohen Ezra E.W. , Lowy Andrew M. , Adams Stephen R. , Advani Sunil J.
Published: April 2023

T-MMAE stability and bystander cytotoxicity in HER2 negative cells.
Supplementary Table S1 from TAS-121, A Selective Mutant EGFR Inhibitor, Shows Activity Against Tumors Expressing Various EGFR Mutations Including T790M and Uncommon Mutations G719X
Authors: Ito Kimihiro , Nishio Makoto , Kato Masanori , Murakami Haruyasu , Aoyagi Yoshimi , Ohe Yuichiro , Okayama Takashige , Hashimoto Akihiro , Ohsawa Hirokazu , Tanaka Gotaro , Nonoshita Katsumasa , Ito Satoru , Matsuo Kenichi , Miyadera Kazutaka
Published: April 2023

Supplementary Table S1 shows kinase selectivity profiling of TAS-121.
Supplementary material and methods and Tables 1-8 from Development of Therapeutic Anti-JAGGED1 Antibodies for Cancer Therapy
Authors: Masiero Massimo , Li Demin , Whiteman Pat , Bentley Carol , Greig Jenny , Hassanali Tasneem , Watts Sarah , Stribbling Stephen , Yates Jenna , Bealing Ellen , Li Ji-Liang , Chillakuri Chandramouli , Sheppard Devon , Serres Sébastien , Sarmiento-Soto Manuel , Larkin James , Sibson Nicola R. , Handford Penny A. , Harris Adrian L. , Banham Alison H.
Published: April 2023

Supplementary material and methods. Supplementary table 1: cell lines and growth conditions. Supplementary table 2: Notch ligands and control protein for plate coating. Supplementary table 3: qPCR primers. Supplementary table 4: flow cytometry antibodies. Supplementary table 5: ICC/IHC antibodies. Supplementary table 6: titration of Notch1-JAG1 binding inhibition by JAG1 antibodies. Supplementary table 7: amino acid sequence of JAG1 antibodies. Supplementary table 8: blood analysis on antibody-treated tumor-bearing rats.
Supplementary Tables S1-S10 from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer
Authors: Naidoo Kalnisha , Wai Patty T. , Maguire Sarah L. , Daley Frances , Haider Syed , Kriplani Divya , Campbell James , Mirza Hasan , Grigoriadis Anita , Tutt Andrew , Moseley Paul M. , Abdel-Fatah Tarek M.A. , Chan Stephen Y.T. , Madhusudan Srinivasan , Rhaka Emad A. , Ellis Ian O. , Lord Christopher J. , Yuan Yinyin , Green Andrew R. , Natrajan Rachael
Published: April 2023

Supplementary Table S1: CDK12 expression in relation to clinicopathological parameters for the unselected TMA series; Supplementary Table S2: CDK12 expression in relation to clinicopathological parameters for the HER2-positive Herceptin treated series; Supplementary Table S3: CDK12 expression in relation to clinicopathological parameters for the METABRIC TMA series; Supplementary Table S4: Univariate and multivariate analysis of CDK12 in the TMA cohorts; Supplementary Table S5: CDK12 mutations in breast cancer. Taken from cBioportal (42,43); Supplementary Table S6: Correlations of CDK12 mutations, methylation, gene expression and ERBB2 copy number in primary breast cancers from TCGA; Supplementary Table S7: Correlations of CDK12 mutations and gene expression of DNA repair genes in primary tumors from METABRIC. P values from heteroscedastic 2-tailed, t-test; Supplementary Table S8: Correlations of CDK12 protein expression, and miRNA expression in primary tumors from METABRIC. Wilcoxon rank P values are corrected for multiple testing; Supplementary Table S9: Correlations of CDK12 protein expression and gene expression of DNA repair genes in primary tumors from METABRIC. Limma analysis corrected for multiple testing; Supplementary Table S10: Association of CDK12 absent and intermediate (0, 2-6) versus high (7-8) expression with DNA repair proteins in unselected and TNBC. P values from Fishers exact test.
Supplementary Tables S1-S26 from A Genome-scale CRISPR Screen Identifies the ERBB and mTOR Signaling Networks as Key Determinants of Response to PI3K Inhibition in Pancreatic Cancer
Authors: Milton Charlotte K. , Self Annette J. , Clarke Paul A. , Banerji Udai , Piccioni Federica , Root David E. , Whittaker Steven R.
Published: April 2023

Tables S1-S26. Includes details of antibodies, shRNAs and sgRNAs used in this study. CRISPR and drug screening data.
Supplementary Materials from A Pilot Study of Galunisertib plus Stereotactic Body Radiotherapy in Patients with Advanced Hepatocellular Carcinoma
Authors: Reiss Kim A. , Wattenberg Max M. , Damjanov Nevena , Prechtel Dunphy Elizabeth , Jacobs-Small Mona , Lubas M. Judy , Robinson James , Dicicco Lisa , Garcia-Marcano Luis , Giannone Michael A. , Karasic Thomas B. , Furth Emma E. , Carpenter Erica L. , Wojcieszynski Andrzej P. , Vonderheide Robert H. , Beatty Gregory L. , Ben-Josef Edgar
Published: April 2023

Supplementary Methods
Supplementary Figure 3 from Therapeutic and Prophylactic Antitumor Activity of an Oral Inhibitor of Fucosylation in Spontaneous Mammary Cancers
Authors: Disis Mary L. , Corulli Lauren R. , Gad Ekram A. , Koehnlein Marlese R. , Cecil Denise L. , Senter Peter D. , Gardai Shyra J. , Okeley Nicole M.
Published: April 2023

Shown is the effect of 2FF treatment on (A) Amount of IgG (Mean {plus minus} SEM) isolated from 75uL of sera collected, and (B) AAL lectin-based measurement of fucosylation (Mean {plus minus} SEM) of these samples from untreated (circle) or 2FF-treated (square) TgMMTV-neu mice (n=5 each).
Supplementary Figure S2 from A Pilot Study of Galunisertib plus Stereotactic Body Radiotherapy in Patients with Advanced Hepatocellular Carcinoma
Authors: Reiss Kim A. , Wattenberg Max M. , Damjanov Nevena , Prechtel Dunphy Elizabeth , Jacobs-Small Mona , Lubas M. Judy , Robinson James , Dicicco Lisa , Garcia-Marcano Luis , Giannone Michael A. , Karasic Thomas B. , Furth Emma E. , Carpenter Erica L. , Wojcieszynski Andrzej P. , Vonderheide Robert H. , Beatty Gregory L. , Ben-Josef Edgar
Published: April 2023

Supervised and unsupervised analysis of peripheral blood leukocyte kinetics
Supplementary Figure S1 from Synthetic Lethality with Trifluridine/Tipiracil and Checkpoint Kinase 1 Inhibitor for Esophageal Squamous Cell Carcinoma
Authors: Ohashi Shinya , Kikuchi Osamu , Nakai Yukie , Ida Tomomi , Saito Tomoki , Kondo Yuki , Yamamoto Yoshihiro , Mitani Yosuke , Nguyen Vu Trang H. , Fukuyama Keita , Tsukihara Hiroshi , Suzuki Norihiko , Muto Manabu
Published: April 2023

The time-course of body-weight changes in mice treated with FTD/TPI and/or prexasertib.
Supplemental Table 3 from Role of Dimerized C16orf74 in Aggressive Pancreatic Cancer: A Novel Therapeutic Target
Authors: Kushibiki Toshihiro , Nakamura Toru , Tsuda Masumi , Tsuchikawa Takahiro , Hontani Koji , Inoko Kazuho , Takahashi Mizuna , Asano Toshimichi , Okamura Keisuke , Murakami Soichi , Kurashima Yo , Ebihara Yuma , Noji Takehiro , Nakanishi Yoshitsugu , Tanaka Kimitaka , Maishi Nako , Sasaki Katsunori , Park Woong-Ryeon , Shichinohe Toshiaki , Hida Kyoko , Tanaka Shinya , Hirano Satoshi
Published: April 2023

The antibodies and dilutions for Immunofluorescence
Supplementary Data Table S1 from An Emerging Landscape for Canonical and Actionable Molecular Alterations in Primary and Metastatic Prostate Cancer
Authors: Dawson Nancy A. , Zibelman Matthew , Lindsay Timothy , Feldman Rebecca A. , Saul Michelle , Gatalica Zoran , Korn W. Michael , Heath Elisabeth I.
Published: April 2023

patient and tumor characteristics
Supplementary Data from Implication of ZNF217 in Accelerating Tumor Development and Therapeutically Targeting ZNF217-Induced PI3K–AKT Signaling for the Treatment of Metastatic Osteosarcoma
Authors: Smeester Branden A. , Draper Garrett M. , Slipek Nicholas J. , Larsson Alex T. , Stratton Natalie , Pomeroy Emily J. , Becklin Kelsie L. , Yamamoto Kenta , Williams Kyle B. , Laoharawee Kanut , Peterson Joseph J. , Abrahante Juan E. , Rathe Susan K. , Mills Lauren J. , Crosby Margaret R. , Hudson Wendy A. , Rahrmann Eric P. , Largaespada David A. , Moriarity Branden S.
Published: April 2023

Antibodies and other reagents utilized
GSEA for decitabine up-regulated genes from Decitabine Response in Breast Cancer Requires Efficient Drug Processing and Is Not Limited by Multidrug Resistance
Authors: Dahn Margaret L. , Cruickshank Brianne M. , Jackson Ainsleigh J. , Dean Cheryl , Holloway Ryan W. , Hall Steven R. , Coyle Krysta M. , Maillet Hillary , Waisman David M. , Goralski Kerry B. , Giacomantonio Carman A. , Weaver Ian C.G. , Marcato Paola
Published: April 2023

Gene Set Enrichment Analysis for genes upregulated by decitabine treatment in MDA-MB-468, MDA-MB-231, or SUM159
Supplementary Table S2 from A Qualitative Transcriptional Signature for Predicting Prognosis and Response to Bevacizumab in Metastatic Colorectal Cancer
Authors: Yang Jing , Song Kai , Guo Wenbing , Zheng Hailong , Fu Yelin , You Tianyi , Wang Kai , Qi Lishuang , Zhao Wenyuan , Guo Zheng
Published: April 2023

Cox univariate and multivariate analysis of all patients in GSE72970 and TCGA.
Supplementary Table S1 from A Qualitative Transcriptional Signature for Predicting Prognosis and Response to Bevacizumab in Metastatic Colorectal Cancer
Authors: Yang Jing , Song Kai , Guo Wenbing , Zheng Hailong , Fu Yelin , You Tianyi , Wang Kai , Qi Lishuang , Zhao Wenyuan , Guo Zheng
Published: April 2023

Composition of the 64 gene pairs (64-GPS)
Supplementary Figure 2 from A Qualitative Transcriptional Signature for Predicting Prognosis and Response to Bevacizumab in Metastatic Colorectal Cancer
Authors: Yang Jing , Song Kai , Guo Wenbing , Zheng Hailong , Fu Yelin , You Tianyi , Wang Kai , Qi Lishuang , Zhao Wenyuan , Guo Zheng
Published: April 2023

The Kaplan-Meier curves of OS for the reclassified response and non-response patients in original groups of TCGA
Supplementary Figure 1 from A Qualitative Transcriptional Signature for Predicting Prognosis and Response to Bevacizumab in Metastatic Colorectal Cancer
Authors: Yang Jing , Song Kai , Guo Wenbing , Zheng Hailong , Fu Yelin , You Tianyi , Wang Kai , Qi Lishuang , Zhao Wenyuan , Guo Zheng
Published: April 2023

The Kaplan-Meier curves of DFS or OS for the reclassified response and non-response patients in original groups of GSE72970.
Table S5 from EMP2 Is a Novel Regulator of Stemness in Breast Cancer Cells
Authors: Dillard Christen , Kiyohara Meagan , Mah Vei , McDermott Sean P. , Bazzoun Dana , Tsui Jessica , Chan Ann M. , Haddad Ghassan , Pellegrini Matteo , Chang Yu-Ling , Elshimali Yahya , Wu Yanyuan , Vadgama Jaydutt V. , Kim Sara R. , Goodglick Lee , Law Samuel M. , Patel Deven D. , Dhawan Puneet , O'Brien Neil A. , Gordon Lynn K. , Braun Jonathan , Lazar Gary , Wicha Max S. , Wadehra Madhuri
Published: April 2023

Secondary tumor formation following anti-EMP2 therapy.
Figure S1-S9 from A Novel Combination Approach Targeting an Enhanced Protein Synthesis Pathway in MYC-driven (Group 3) Medulloblastoma
Authors: Chaturvedi Nagendra K. , Kling Matthew J. , Griggs Connor N. , Kesherwani Varun , Shukla Mamta , McIntyre Erin M. , Ray Sutapa , Liu Yutong , McGuire Timothy R. , Sharp J. Graham , Band Hamid , Joshi Shantaram S. , Coulter Don W.
Published: April 2023

Fig. S1. RNA-seq analysis between MYC vs non-MYC amplified MB cell lines. Fig. S2. Synergistic effects of OTX and mTOR inhibitors on MYC-amplified MB cell growth. Fig. S3. JQ1 chemosensitizes the MB cells. Fig. S4. Flow cytometry plots for cell cycle distribution (as summarized in main Fig. 2A and 2D) in MB cell lines-treated with inhibitors alone or combined as indicated. Fig. S5. The representative Annexin-V flow plots for apoptosis (as summarized in main Fig. 2C and 2E) in HD-MB03 MB cell lines-treated with inhibitors alone or combined as indicated. Fig. S6. Combination effects of BET protein inhibitor OTX with mTOR inhibitors (BEZ/TEM) on cell cycle and apoptosis in MYC-driven HD-MB03 cells. Fig. S7. Combination effects of JQ1/BEZ or JQ1/TEM on associated pathways/molecules. Fig. S8. Effects of inhibitors on body weight and histology of the MB xenograft mice. Fig. S9. Combined in vivo effects of JQ1 and BEZ on the expression levels of target key proteins using subcutaneous MYC-amplified MB xenografts.
Supplementary Figure from Exploiting Ligand-binding Domain Dimerization for Development of Novel Androgen Receptor Inhibitors
Authors: Helsen Christine , Nguyen Tien T. , Lee Xiao Yin , Eerlings Roy , Louros Nikolaos , Schymkowitz Joost , Rousseau Frederic , Claessens Frank , Voet Arnout
Published: April 2023

Supplementary Figure from Exploiting Ligand-binding Domain Dimerization for Development of Novel Androgen Receptor Inhibitors
Supplementary Table from Luxeptinib (CG-806) Targets FLT3 and Clusters of Kinases Operative in Acute Myeloid Leukemia
Authors: Rice William G. , Howell Stephen B. , Zhang Hongying , Rastgoo Nasrin , Local Andrea , Kurtz Stephen E. , Lo Pierrette , Bottomly Daniel , Wilmot Beth , McWeeney Shannon K. , Druker Brian J. , Tyner Jeffrey W.
Published: April 2023

Supplementary Table from Luxeptinib (CG-806) Targets FLT3 and Clusters of Kinases Operative in Acute Myeloid Leukemia
Supplementary Data from Ubiquitinated PCNA Drives USP1 Synthetic Lethality in Cancer
Authors: Simoneau Antoine , Engel Justin L. , Bandi Madhavi , Lazarides Katherine , Liu Shangtao , Meier Samuel R. , Choi Ashley H. , Zhang Hongxiang , Shen Binzhang , Martires Lauren , Gotur Deepali , Pham Truc V. , Li Fang , Gu Lina , Gong Shanzhong , Zhang Minjie , Wilker Erik , Pan Xuewen , Whittington Douglas A. , Throner Scott , Maxwell John P. , Chen Yingnan , Yu Yi , Huang Alan , Andersen Jannik N. , Feng Tianshu
Published: April 2023

Supplementary methods
Supplementary Figure from Inhibition of NF-κB DNA Binding Suppresses Myeloma Growth via Intracellular Redox and Tumor Microenvironment Modulation
Authors: Bariana Manpreet , Cassella Elena , Rateshwar Janice , Ouk Samedy , Liou Hsiou-Chi , Heller Claudia , Colorado Iriana , Feinman Rena , Makhdoom Ali , Siegel David S. , Heller Glenn , Tuckett Andrea , Mondello Patrizia , Zakrzewski Johannes L.
Published: April 2023

Supplementary Figure from Inhibition of NF-κB DNA Binding Suppresses Myeloma Growth via Intracellular Redox and Tumor Microenvironment Modulation
Supplementary Data from Suppression of Chromosome Instability Limits Acquired Drug Resistance
Authors: Crowley Elizabeth A. , Hermance Nicole M. , Herlihy Conor P. , Manning Amity L.
Published: April 2023

Supplementary Data from Suppression of Chromosome Instability Limits Acquired Drug Resistance
Supplementary Figure from IDO1 Is a Therapeutic Target for Pancreatic Cancer–Associated Depression
Authors: Hue Jonathan J. , Graor Hallie J. , Zarei Mehrdad , Katayama Erryk S. , Ji Karen , Hajihassani Omid , Loftus Alexander W. , Vaziri-Gohar Ali , Winter Jordan M.
Published: April 2023

Supplementary Figure from IDO1 Is a Therapeutic Target for Pancreatic Cancer–Associated Depression
Supplementary Figure from Sirpiglenastat (DRP-104) Induces Antitumor Efficacy through Direct, Broad Antagonism of Glutamine Metabolism and Stimulation of the Innate and Adaptive Immune Systems
Authors: Yokoyama Yumi , Estok Thomas M. , Wild Robert
Published: April 2023

Supplementary Figure from Sirpiglenastat (DRP-104) Induces Antitumor Efficacy through Direct, Broad Antagonism of Glutamine Metabolism and Stimulation of the Innate and Adaptive Immune Systems
Supplementary Data from Establishment and Evaluation of Dual HDAC/BET Inhibitors as Therapeutic Options for Germ Cell Tumors and Other Urological Malignancies
Authors: Burmeister Aaron , Stephan Alexa , Alves Avelar Leandro A. , Müller Melanie R. , Seiwert Andrea , Höfmann Stefan , Fischer Fabian , Torres-Gomez Hector , Hoffmann Michèle J. , Niegisch Guenter , Bremmer Felix , Petzsch Patrick , Köhrer Karl , Albers Peter , Kurz Thomas , Skowron Margaretha A. , Nettersheim Daniel
Published: April 2023

Supplementary Data from Establishment and Evaluation of Dual HDAC/BET Inhibitors as Therapeutic Options for Germ Cell Tumors and Other Urological Malignancies
Supplementary Data from Daclatasvir, an Antiviral Drug, Downregulates Tribbles 2 Pseudokinase and Resensitizes Enzalutamide-Resistant Prostate Cancer Cells
Authors: Monga Jitender , Valeriote Frederick , Hwang Clara , Gadgeel Shirish , Ghosh Jagadananda
Published: April 2023

Supplementary Figures 1-2
Supplementary Figure from BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors
Authors: Rigby Michael , Bennett Gavin , Chen Liuhong , Mudd Gemma E. , Harrison Helen , Beswick Paul J. , Van Rietschoten Katerine , Watcham Sophie M. , Scott Heather S. , Brown Amy N. , Park Peter U. , Campbell Carly , Haines Eric , Lahdenranta Johanna , Skynner Michael J. , Jeffrey Phil , Keen Nicholas , Lee Kevin
Published: April 2023

Supplementary Figure from BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors
Supplementary Figures from High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer
Authors: Mizuno Sho , Ikegami Masachika , Koyama Takafumi , Sunami Kuniko , Ogata Dai , Kage Hidenori , Yanagaki Mitsuru , Ikeuchi Hiroshi , Ueno Toshihide , Tanikawa Michihiro , Oda Katsutoshi , Osuga Yutaka , Mano Hiroyuki , Kohsaka Shinji
Published: April 2023

Figure S1 to S17
Supplementary Figure from Demonstration of the Antitumor Activity of the iNKT Agonist ABX196, a Novel Enhancer of Cancer Immunotherapy, in Melanoma and Hepatocarcinoma Mouse Models
Authors: Scherrer Didier , Barrett Noel , Teyton Luc , Pearce Tillman , Nitcheu Josianne , Pouletty Philippe , Santo Julien , Ehrlich Hartmut J.
Published: April 2023

Supplementary Figure from Demonstration of the Antitumor Activity of the iNKT Agonist ABX196, a Novel Enhancer of Cancer Immunotherapy, in Melanoma and Hepatocarcinoma Mouse Models
Figure S9 from Inhibition of LILRB2 by a Novel Blocking Antibody Designed to Reprogram Immunosuppressive Macrophages to Drive T-Cell Activation in Tumors
Authors: Umiker Ben , Hashambhoy-Ramsay Yasmin , Smith Jeff , Rahman Tanzila , Mueller Amy , Davidson Rachel , Meyer Christina , Patankar Gayatri , Alam Mohammad Murshid , Jaffe Sarah , Krukenberg Kristin , Goodman Allison , Spaulding Vikki , Priess Michelle , Dhaneshwar Abha , Wong Masie , Diiorio Alexa , O'Malley Kristin , McGrath Lara , Willer Margaret , Pepper Lauren , Gostissa Monica , Kis-Toth Katalin , Wiederschain Dmitri , Cohen Heather , Shaffer Donald R.
Published: April 2023

Sensitivity of LILRB2 as a predictive biomarker for pharmacodynamic response as measured by the macrophage polarization score in histoculture explant cultures.
Supplementary Data from Identification of IGF2 as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma
Authors: Abril-Fornaguera Jordi , Torrens Laura , Andreu-Oller Carmen , Carrillo-Reixach Juan , Rialdi Alex , Balaseviciute Ugne , Pinyol Roser , Montironi Carla , Haber Philipp K. , Del Río-Álvarez Álvaro , Domingo-Sàbat Montserrat , Royo Laura , Akers Nicholas K. , Willoughby Catherine E. , Peix Judit , Torres-Martin Miguel , Puigvehi Marc , Cairo Stefano , Childs Margaret , Maibach Rudolf , Alaggio Rita , Czauderna Piotr , Morland Bruce , Losic Bojan , Mazzaferro Vincenzo , Guccione Ernesto , Sia Daniela , Armengol Carolina , Llovet Josep M.
Published: April 2023

Supplementary Figures and Tables
Supplementary Materials & Methods from Griseofulvin Radiosensitizes Non–Small Cell Lung Cancer Cells and Activates cGAS
Authors: Wang Xing , Raman Natasha , Lemtiri-Chlieh Ghali , Chang Jinhee , Jagtap Shreya , Chowdhury Dipanwita Dutta , Ballew Matthew , Carrieri Francesca Anna , Nguyen Triet , Nugent Katriana , Peck Travis , Levine Michelle S. , Chan Aaron , Lam Christine , Malek Reem , Hoang Tung , Phillips Ryan , Cheng ZhuoAn , Taparra Kekoa , Connis Nick , Hann Christine L. , Holland Andrew , Tran Phuoc T. , Lafargue Audrey , Wang Hailun
Published: April 2023

Supplementary Materials & Methods
Data from GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 Expression
Authors: Cucchiara Vito , Yang Joy C. , Liu Chengfei , Adomat Hans H. , Tomlinson Guns Emma S. , Gleave Martin E. , Gao Allen C. , Evans Christopher P.
Published: April 2023

Abstract
Hormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. Degarelix (Firmagon), a gonadotropin-releasing hormone (GnRH) receptor antagonist differs from luteinizing hormone-releasing hormone (LHRH) agonists by avoiding “testosterone flare” and lower follicle-stimulating hormone (FSH) levels. The direct effect of degarelix and leuprolide on human prostate cancer cells was evaluated. In LNCaP, C4-2BMDVR, and CWR22Rv1 cells, degarelix significantly reduced cell viability compared with the controls (P ≤ 0.01). Leuprolide was stimulatory in the same cell lines. In C4-2B MDVR cells, degarelix alone or combined with abiraterone or enzalutamide reduced the AR-V7 protein expression compared with the control group. SCID mice bearing VCaP xenograft tumors were divided into 4 groups and treated with surgical castration, degarelix, leuprolide, or buffer alone for 4 weeks. Leuprolide slightly suppressed tumor growth compared with the vehicle control group (P > 0.05). Tumors in degarelix-treated mice were 67% of those in the leuprolide-treatment group but 170% larger than in surgically castrated ones. Measurements of intratumoral steroids in serum, tumor samples, or treated cell pellets by LC/MS confirmed that degarelix better decreased the levels of testosterone and steroidogenesis pathway intermediates, comparable to surgical castration, whereas leuprolide had no inhibitory effect. Collectively, our results suggested a selective mechanism of action of degarelix against androgen steroidogenesis and AR-variants. This study provides additional molecular insights regarding the mechanism of degarelix compared with GnRH agonist therapy, which may have clinical implications.
Data from XPO1 Inhibitor Selinexor Overcomes Intrinsic Ibrutinib Resistance in Mantle Cell Lymphoma via Nuclear Retention of IκB
Authors: Ming Mei , Wu Wenjun , Xie Bingqing , Sukhanova Madina , Wang Weige , Kadri Sabah , Sharma Shruti , Lee Jimmy , Shacham Sharon , Landesman Yosef , Maltsev Natalia , Lu Pin , Wang Y. Lynn
Published: April 2023

Abstract
Inhibition of B-cell receptor (BCR) signaling through the BTK inhibitor, ibrutinib, has generated a remarkable response in mantle cell lymphoma (MCL). However, approximately one third of patients do not respond well to the drug, and disease relapse on ibrutinib is nearly universal. Alternative therapeutic strategies aimed to prevent and overcome ibrutinib resistance are needed. We compared and contrasted the effects of selinexor, a selective inhibitor of nuclear export, with ibrutinib in six MCL cell lines that display differential intrinsic sensitivity to ibrutinib. We found that selinexor had a broader antitumor activity in MCL than ibrutinib. MCL cell lines resistant to ibrutinib remained sensitive to selinexor. We showed that selinexor induced apoptosis/cell-cycle arrest and XPO-1 knockdown also retarded cell growth. Furthermore, downregulation of the NFκB gene signature, as opposed to BCR signature, was a common feature that underlies the response of MCL to both selinexor and ibrutinib. Meanwhile, unaltered NFκB was associated with ibrutinib resistance. Mechnistically, selinexor induced nuclear retention of IκB that was accompanied by the reduction of DNA-binding activity of NFκB, suggesting that NFκB is trapped in an inhibitory complex. Coimmunoprecipitation confirmed that p65 of NFκB and IκB were physically associated. In primary MCL tumors, we further demonstrated that the number of cells with IκB nuclear retention was linearly correlated with the degree of apoptosis. Our data highlight the role of NFκB pathway in drug response to ibrutinib and selinexor and show the potential of using selinexor to prevent and overcome intrinsic ibrutinib resistance through NFκB inhibition.
Data from MORAb-202, an Antibody–Drug Conjugate Utilizing Humanized Anti-human FRα Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity
Authors: Cheng Xin , Li Jing , Tanaka Keigo , Majumder Utpal , Milinichik Andrew Z. , Verdi Arielle C. , Maddage Christopher J. , Rybinski Katherine A. , Fernando Shawn , Fernando Danielle , Kuc Megan , Furuuchi Keiji , Fang Frank , Uenaka Toshimitsu , Grasso Luigi , Albone Earl F.
Published: April 2023

Abstract
Microtubule-targeting agents (MTA) have been investigated for many years as payloads for antibody–drug conjugates (ADC). In many cases, these ADCs have shown limited benefits due to lack of efficacy or significant toxicity, which has spurred continued investigation into novel MTA payloads for next-generation ADCs. In this study, we have developed ADCs using the MTA eribulin, a derivative of the macrocyclic polyether natural product halichondrin B, as a payload. Eribulin ADCs demonstrated in vitro potency and specificity using various linkers and two different conjugation approaches. MORAb-202 is an investigational agent that consists of the humanized anti-human folate receptor alpha (FRA) antibody farletuzumab conjugated via reduced interchain disulfide bonds to maleimido-PEG2-valine-citrulline-p-aminobenzylcarbamyl-eribulin at a drug-to-antibody ratio of 4.0. MORAb-202 displayed preferable biophysical properties and broad potency across a number of FRA-positive tumor cell lines as well as demonstrated improved specificity in vitro compared with farletuzumab conjugated with a number of other MTA payloads, including MMAE, MMAF, and the reducible maytansine linker-payload sulfo-SPDB-DM4. A single-dose administration of MORAb-202 in FRA-positive human tumor cell line xenograft and patient-derived tumor xenograft models elicited a robust and durable antitumor response. These data support further investigation of MORAb-202 as a potential new treatment modality for FRA-positive cancers, using the novel MTA eribulin as a payload.
Data from Phyllanthusmin Derivatives Induce Apoptosis and Reduce Tumor Burden in High-Grade Serous Ovarian Cancer by Late-Stage Autophagy Inhibition
Authors: Young Alexandria N. , Herrera Denisse , Huntsman Andrew C. , Korkmaz Melissa A. , Lantvit Daniel D. , Mazumder Sarmistha , Kolli Shamalatha , Coss Christopher C. , King Salane , Wang Hongyan , Swanson Steven M. , Kinghorn A. Douglas , Zhang Xiaoli , Phelps Mitch A. , Aldrich Leslie N. , Fuchs James R. , Burdette Joanna E.
Published: April 2023

Abstract
High-grade serous ovarian cancer (HGSOC) is a lethal gynecological malignancy with a need for new therapeutics. Many of the most widely used chemotherapeutic drugs are derived from natural products or their semi-synthetic derivatives. We have developed potent synthetic analogues of a class of compounds known as phyllanthusmins, inspired by natural products isolated from Phyllanthus poilanei Beille. The most potent analogue, PHY34, had the highest potency in HGSOC cell lines in vitro and displayed cytotoxic activity through activation of apoptosis. PHY34 exerts its cytotoxic effects by inhibiting autophagy at a late stage in the pathway, involving the disruption of lysosomal function. The autophagy activator, rapamycin, combined with PHY34 eliminated apoptosis, suggesting that autophagy inhibition may be required for apoptosis. PHY34 was readily bioavailable through intraperitoneal administration in vivo where it significantly inhibited the growth of cancer cell lines in hollow fibers, as well as reduced tumor burden in a xenograft model. We demonstrate that PHY34 acts as a late-stage autophagy inhibitor with nanomolar potency and significant antitumor efficacy as a single agent against HGSOC in vivo. This class of compounds holds promise as a potential, novel chemotherapeutic and demonstrates the effectiveness of targeting the autophagic pathway as a viable strategy for combating ovarian cancer. Mol Cancer Ther; 17(10); 2123–35. ©2018 AACR.
Data from Selective Inhibition of the Lactate Transporter MCT4 Reduces Growth of Invasive Bladder Cancer
Authors: Todenhöfer Tilman , Seiler Roland , Stewart Craig , Moskalev Igor , Gao Jian , Ladhar Simroop , Kamjabi Alireza , Al Nakouzi Nader , Hayashi Tetsuharo , Choi Stephen , Wang Yuzhuo , Frees Sebastian , Daugaard Mads , Oo Htoo Zarni , Fisel Pascale , Schwab Matthias , Schaeffeler Elke , Douglas James , Hennenlotter Jörg , Bedke Jens , Gibb Ewan A. , Fazli Ladan , Stenzl Arnulf , Black Peter C.
Published: April 2023

Abstract
The significance of lactate transporters has been recognized in various cancer types, but their role in urothelial carcinoma remains mostly unknown. The aim of this study was to investigate the functional importance of the monocarboxylate transporter (MCT) 4 in preclinical models of urothelial carcinoma and to assess its relevance in patient tumors. The association of MCT4 expression with molecular subtypes and outcome was determined in The Cancer Genome Atlas (TCGA) cohort and two independent cohorts of patients with urothelial carcinoma. Silencing of MCT4 was performed using siRNAs in urothelial carcinoma cell lines. Effects of MCT4 inhibition on cell growth, apoptosis, and production of reactive oxygen species (ROS) were assessed. Moreover, effects on lactate efflux were determined. The in vivo effects of MCT4 silencing were assessed in an orthotopic xenograft model. MCT4 expression was higher in the basal subtype. Decreased MCT4 methylation and increased RNA and protein expression were associated with worse overall survival (OS). Inhibition of MCT4 led to a reduction in cell growth, induction of apoptosis, and an increased synthesis of ROS. MCT4 inhibition resulted in intracellular accumulation of lactate. In vivo, stable knockdown of MCT4 reduced tumor growth. The expression of MCT4 in urothelial carcinoma is associated with features of aggressive tumor biology and portends a poor prognosis. Inhibition of MCT4 results in decreased tumor growth in vitro and in vivo. Targeting lactate metabolism via MCT4 therefore provides a promising therapeutic approach for invasive urothelial carcinoma, especially in the basal subtype.