bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Table 2 from The Selective Anaplastic Lymphoma Receptor Tyrosine Kinase Inhibitor ASP3026 Induces Tumor Regression and Prolongs Survival in Non–Small Cell Lung Cancer Model Mice
Authors: Mori Masamichi , Ueno Yoko , Konagai Satoshi , Fushiki Hiroshi , Shimada Itsuro , Kondoh Yutaka , Saito Rika , Mori Kenichi , Shindou Nobuaki , Soga Takatoshi , Sakagami Hideki , Furutani Takashi , Doihara Hitoshi , Kudoh Masafumi , Kuromitsu Sadao
Published: April 2023

PDF file - 64K, Inhibition of ALK phosphorylation and signal transduction in NCI-H2228 cells by ASP3026.
Supplementary Figures 1-9; Supplementary Table 1 from The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation
Authors: Cerniglia George J. , Dey Souvik , Gallagher-Colombo Shannon M. , Daurio Natalie A. , Tuttle Stephen , Busch Theresa M. , Lin Alexander , Sun Ramon , Esipova Tatiana V. , Vinogradov Sergei A. , Denko Nicholas , Koumenis Constantinos , Maity Amit
Published: April 2023

Supplementary Figures 1-9; Supplementary Table 1. Suppl. Fig. 1 Western blotting for downstream targets of PI3K and mTOR. Suppl. Fig. 2 Effect of dual PI3K/mTOR inhibitors on OCR. Suppl. Fig. 3 Effect of BEZ235 on mitochondrial mass and membrane potential. Suppl. Fig. 4 Analysis of the COX1 DNA levels by RT-PCR. Suppl. Fig. 5 Effect of dual PI3K/mTOR inhibitors on PDH complex subunits. Suppl. Fig. 6 Effects on OCR following the treatment with inhibitors of Akt and/or PI3K. Suppl. Fig. 7 Relationship between PI3K activation and PDH-E1α phosphorylation using doxycycline-inducible system. Suppl. Fig. 8 Effect of PDH-E1α inhibition on OCR. Suppl. Fig. 9 Effect of PDH-E1α mutants on PDH-E1α phosphorylation. Table S1 Sequence of primers used to measure the levels of the COX1 and PNC1.
Supplementary Figure 4 from Myostatin Neutralization Results in Preservation of Muscle Mass and Strength in Preclinical Models of Tumor-Induced Muscle Wasting
Authors: Smith Rosamund C. , Cramer Martin S. , Mitchell Pamela J. , Capen Andrew , Huber Lysiane , Wang Rong , Myers Laura , Jones Bryan E. , Eastwood Brian J. , Ballard Darryl , Hanson Jeff , Credille Kelly M. , Wroblewski Victor J. , Lin Boris K. , Heuer Josef G.
Published: April 2023

Supplementary Figure 4. LY2495655 attenuates loss of muscle weight normalized to brain weight but has no effect on brain or heart weight in C26 tumor bearing mice in the presence of gemcitabine.
Supplementary Figures 1-2 from NT113, a Pan-ERBB Inhibitor with High Brain Penetrance, Inhibits the Growth of Glioblastoma Xenografts with EGFR Amplification
Authors: Yoshida Yasuyuki , Ozawa Tomoko , Yao Tsun-Wen , Shen Wang , Brown Dennis , Parsa Andrew T. , Raizer Jeffrey J. , Cheng Shi-Yuan , Stegh Alexander H. , Mazar Andrew P. , Giles Francis J. , Sarkaria Jann N. , Butowski Nicholas , Nicolaides Theodore , James C. David
Published: April 2023

Supplementary Figure 1: NT113 Chemical Structure; Supplementary Figure 2: A) Relative expression of endogenous wild-type EGFR in parental U87 cells (U87p) vs. U87 cells transduced with EGFRvIII retrovirus (U87vIII). B) Relative expression of EGFRwt, EGFRvIII, ERBB2 and ERBB4 in subcutaneous tumors of GBM12, GBM39, and GBM6.
Figure S2 from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway
Authors: Dhanyamraju Pavan Kumar , Holz Philipp Simon , Finkernagel Florian , Fendrich Volker , Lauth Matthias
Published: April 2023

This file contains various control experiments such as siRNA validation, impact on cell toxicity or the effects of HDAC6 knock-down on the expression of other HDAC family members.
Supplementary Table 1, Supplementary Table 2A, Supplementary Table 2B, Supplementary Table 3, Supplementary Table 4, or Supplementary Table 5 from TWIST1 Polymorphisms Predict Survival in Patients with Metastatic Colorectal Cancer Receiving First-Line Bevacizumab plus Oxaliplatin-Based Chemotherapy
Authors: Matsusaka Satoshi , Zhang Wu , Cao Shu , Hanna Diana L. , Sunakawa Yu , Sebio Ana , Ueno Masashi , Yang Dongyun , Ning Yan , Parekh Anish , Okazaki Satoshi , Berger Martin D. , Ichikawa Wataru , Mizunuma Nobuyuki , Lenz Heinz-Josef
Published: April 2023

Supplementary Table 1. Summary of EMT-related SNPs Supplementary Table 2A. Association between baseline characteristics and clinical outcomes in the bevacizumab cohort Supplementary Table 2B. Association between baseline characteristics and clinical outcomes in the cetuximab cohort Supplementary Table 3. Association between TWIST1 rs2285682 and clinical outcomes in KRAS wild-type and mutant subgroups among the bevacizumab cohort Supplementary Table 4. Association between EMT-related SNPs and clinical outcomes stratified by gender in the bevacizumab cohort Supplementary Table 5. Association between TWIST1 rs2285682 and clinical outcomes in the cetuximab cohort
Supplementary Figure 3 from Response to MLN8237 in Pancreatic Cancer Is Not Dependent on RalA Phosphorylation
Authors: Neel Nicole F. , Stratford Jeran K. , Shinde Vaishali , Ecsedy Jeffrey A. , Martin Timothy D. , Der Channing J. , Yeh Jen Jen
Published: April 2023

PDF - 1287K, pRalA changes in tumors.
Supplementary Figure 2 from Dual Targeting of Bromodomain and Extraterminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells
Authors: Tögel Lars , Nightingale Rebecca , Chueh Anderly C. , Jayachandran Aparna , Tran Hoanh , Phesse Toby , Wu Rui , Sieber Oliver M. , Arango Diego , Dhillon Amardeep S. , Dawson Mark A. , Diez-Dacal Beatriz , Gahman Timothy C. , Filippakopoulos Panagis , Shiau Andrew K. , Mariadason John M.
Published: April 2023

BET protein expression in primary colorectal cancers.
Suppllementary Methods and Supplementary Figures 1-5 from BET Inhibition Induces Apoptosis in Aggressive B-Cell Lymphoma via Epigenetic Regulation of BCL-2 Family Members
Authors: Hogg Simon J. , Newbold Andrea , Vervoort Stephin J. , Cluse Leonie A. , Martin Benjamin P. , Gregory Gareth P. , Lefebure Marcus , Vidacs Eva , Tothill Richard W. , Bradner James E. , Shortt Jake , Johnstone Ricky W.
Published: April 2023

Supplementary Methods, Supplementary References, Supplementary Figure 1 - in vitro analysis of various BET inhibitors against Eu-myc lymphoma cells and effect of JQ1 on OPM2 and OPM2/BCL2 cells; Supplementary Figure 2 - In vitro effects of JQ1 on OPM2 and OPM2/BCL2 cells; Supplementary Figure 3 - In vivo effects of JQ1 showing lack of toxicity; Supplementary Figure 4 - induction of Bim in JQ1-sensitive and JQ1-resistant Eu-myc lymphomas; Supplementary Figure 5 - Activated Ras confers resistance to JAK inhibitor and JQ1.
Supplementary Video 6 from A Murine Model for Quantitative, Real-Time Evaluation of Convection-Enhanced Delivery (RT-CED) Using an 18[F]-Positron Emitting, Fluorescent Derivative of Dasatinib
Authors: Wang Melinda , Kommidi Harikrishna , Tosi Umberto , Guo Hua , Zhou Zhiping , Schweitzer Melanie E. , Wu Linda Y. , Singh Ranjodh , Hou Shengqi , Law Benedict , Ting Richard , Souweidane Mark M.
Published: April 2023

Supporting Video S6. Horizontal PET(red)/CT(blue) projection showing dynamic, systemic (tail-vein) delivery of [18F]-1. PET is overexposed in attempts to capture drug presence in the brain volume. (Video of Fig.4Aiv and v)
Table S3 from Receptor Tyrosine Kinase Phosphorylation Pattern–Based Multidrug Combination Is an Effective Approach for Personalized Cancer Treatment
Authors: Sun Xiaoxiao , Song Qiaoling , He Li , Yan Lei , Liu Jingli , Zhang Qing , Yu Qiang
Published: April 2023

Analysis of RTK arrays in literature (primary patient samples).
Supplementary Figure S4 from EZH2 Inhibition Blocks Multiple Myeloma Cell Growth through Upregulation of Epithelial Tumor Suppressor Genes
Authors: Hernando Henar , Gelato Kathy A. , Lesche Ralf , Beckmann Georg , Koehr Silke , Otto Saskia , Steigemann Patrick , Stresemann Carlo
Published: April 2023

Effects of GSK126 treatment in MOLP-8 cell line
Supplementary Figure Legends, Supplementary Figures 1 and 2 and Supplementary Table 1 from Antitumor Effects of Immunotoxins Are Enhanced by Lowering HCK or Treatment with Src Kinase Inhibitors
Authors: Liu Xiu-Fen , Xiang Laiman , FitzGerald David J. , Pastan Ira
Published: April 2023

PDF - 950KB, Legends for Supplementary Figures 1 and 2; Supplementary Figure 1: Screening of TK siRNA library; Supplementary Figure2: Src knock down slightly increased SS1P toxicity; Supplementary Table 1: Oligos used in the study.
Supplementary Figure S3 from Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer
Authors: Kato Akihisa , Kataoka Hiromi , Yano Shigenobu , Hayashi Kazuki , Hayashi Noriyuki , Tanaka Mamoru , Naitoh Itaru , Ban Tesshin , Miyabe Katsuyuki , Kondo Hiromu , Yoshida Michihiro , Fujita Yasuaki , Hori Yasuki , Natsume Makoto , Murakami Takashi , Narumi Atsushi , Nomoto Akihiro , Naiki-Ito Aya , Takahashi Satoru , Joh Takashi
Published: April 2023

Average body weight transitions of mice during the experiment.
Supplementary Figure S2 from Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer
Authors: Kato Akihisa , Kataoka Hiromi , Yano Shigenobu , Hayashi Kazuki , Hayashi Noriyuki , Tanaka Mamoru , Naitoh Itaru , Ban Tesshin , Miyabe Katsuyuki , Kondo Hiromu , Yoshida Michihiro , Fujita Yasuaki , Hori Yasuki , Natsume Makoto , Murakami Takashi , Narumi Atsushi , Nomoto Akihiro , Naiki-Ito Aya , Takahashi Satoru , Joh Takashi
Published: April 2023

The luciferase luminescence intensities in AsPC1/luc cells treated by PDT with talaporfin or Mal3-chlorin.
Supplementary Figure Legend from Characterization of EGFR T790M, L792F, and C797S Mutations as Mechanisms of Acquired Resistance to Afatinib in Lung Cancer
Authors: Kobayashi Yoshihisa , Azuma Koichi , Nagai Hiroki , Kim Young Hak , Togashi Yosuke , Sesumi Yuichi , Chiba Masato , Shimoji Masaki , Sato Katsuaki , Tomizawa Kenji , Takemoto Toshiki , Nishio Kazuto , Mitsudomi Tetsuya
Published: April 2023

Legend for supplementary figures.
Supplementary Figure 2 from Characterization of EGFR T790M, L792F, and C797S Mutations as Mechanisms of Acquired Resistance to Afatinib in Lung Cancer
Authors: Kobayashi Yoshihisa , Azuma Koichi , Nagai Hiroki , Kim Young Hak , Togashi Yosuke , Sesumi Yuichi , Chiba Masato , Shimoji Masaki , Sato Katsuaki , Tomizawa Kenji , Takemoto Toshiki , Nishio Kazuto , Mitsudomi Tetsuya
Published: April 2023

Growth inhibitory curves of Ba/F3 cells expressing EGFR L792F
'Supplementary Methods' from Genomic and Molecular Screenings Identify Different Mechanisms for Acquired Resistance to MET Inhibitors in Lung Cancer Cells
Authors: Gimenez-Xavier Pol , Pros Eva , Bonastre Ester , Moran Sebastian , Aza Ana , Graña Osvaldo , Gomez-Lopez Gonzalo , Derdak Sophia , Dabad Marc , Esteve-Codina Anna , Hernandez Mora Jose R. , Salinas-Chaparro Diana , Esteller Manel , Pisano David , Sanchez-Cespedes Montse
Published: April 2023

'Supplementary Methods'
Supplementary Table 4 from ATR Inhibition Is a Promising Radiosensitizing Strategy for Triple-Negative Breast Cancer
Authors: Tu Xinyi , Kahila Mohamed M. , Zhou Qin , Yu Jia , Kalari Krishna R. , Wang Liewei , Harmsen William S. , Yuan Jian , Boughey Judy C. , Goetz Matthew P. , Sarkaria Jann N. , Lou Zhenkun , Mutter Robert W.
Published: April 2023

Supplementary Table 4 demonstrates single nucleotide variants, indels, copy number variants and copy number alterations in MCTNBC4
Supplementary Table 3 from ATR Inhibition Is a Promising Radiosensitizing Strategy for Triple-Negative Breast Cancer
Authors: Tu Xinyi , Kahila Mohamed M. , Zhou Qin , Yu Jia , Kalari Krishna R. , Wang Liewei , Harmsen William S. , Yuan Jian , Boughey Judy C. , Goetz Matthew P. , Sarkaria Jann N. , Lou Zhenkun , Mutter Robert W.
Published: April 2023

Supplementary Table 3 demonstrates single nucleotide variants, indels, copy number variants and copy number alterations in MCTNBC3
Supplemental Figure 1 from Preclinical Evaluation of Nintedanib, a Triple Angiokinase Inhibitor, in Soft-tissue Sarcoma: Potential Therapeutic Implication for Synovial Sarcoma
Authors: Patwardhan Parag P. , Musi Elgilda , Schwartz Gary K.
Published: April 2023

Western blot analysis for RTK and non-RTK targets
Supplementary Figure S5 from Combined MEK and BCL-2/XL Inhibition Is Effective in High-Grade Serous Ovarian Cancer Patient–Derived Xenograft Models and BIM Levels Are Predictive of Responsiveness
Authors: Iavarone Claudia , Zervantonakis Ioannis K. , Selfors Laura M. , Palakurthi Sangeetha , Liu Joyce F. , Drapkin Ronny , Matulonis Ursula A. , Hallberg Dorothy , Velculescu Victor E. , Leverson Joel D. , Sampath Deepak , Mills Gordon B. , Brugge Joan S.
Published: April 2023

Supplementary Figure S5 describes the Correlation of positive predictors before and after MEK inhibition; validation of BIM as a predictor of drug response in an independent set of ovarian cancer cell lines; predictive model including baseline levels of BIM and pERK
Figure S3 from Mechanisms of Entrectinib Resistance in a Neuroblastoma Xenograft Model
Authors: MacFarland Suzanne P. , Naraparaju Koumudi , Iyer Radhika , Guan Peng , Kolla Venkatadri , Hu Yuxuan , Tan Kai , Brodeur Garrett M.
Published: April 2023

Principle Components Analysis (PCA) of entrectinib resistant cell lines showing clustering of resistant cell lines as compared to parental cell line
Figure S3 from HSP90 Inhibitor–SN-38 Conjugate Strategy for Targeted Delivery of Topoisomerase I Inhibitor to Tumors
Authors: Proia David A. , Smith Donald L. , Zhang Junyi , Jimenez John-Paul , Sang Jim , Ogawa Luisa Shin , Sequeira Manuel , Acquaviva Jaime , He Suqin , Zhang Chaohua , Khazak Vladimir , Astsaturov Igor , Inoue Takayo , Tatsuta Noriaki , Osman Sami , Bates Richard C. , Chimmanamada Dinesh , Ying Weiwen
Published: April 2023

Kinetic analysis of p-KAP1 induction in MDA-MB-231 xenograft tumors.
Figure S1 from Plk1 Inhibition Enhances the Efficacy of BET Epigenetic Reader Blockade in Castration-Resistant Prostate Cancer
Authors: Mao Fengyi , Li Jie , Luo Qian , Wang Ruixin , Kong Yifan , Carlock Colin , Liu Zian , Elzey Bennet D. , Liu Xiaoqi
Published: April 2023

Quantification results of colony formation and Annexin V/PI staining
Supplemental figure 5 from Antitumor Effects of MEHD7945A, a Dual-Specific Antibody against EGFR and HER3, in Combination with Radiation in Lung and Head and Neck Cancers
Authors: Li Chunrong , Huang Shyhmin , Armstrong Eric A. , Francis David M. , Werner Lauryn R. , Sliwkowski Mark X. , van der Kogel Albert , Harari Paul M.
Published: April 2023

MEHD7945A affects the vasculature in tumor xenografts.
Figure S4 from TTK Inhibitors as a Targeted Therapy for CTNNB1 (β-catenin) Mutant Cancers
Authors: Zaman Guido J.R. , de Roos Jeroen A.D.M. , Libouban Marion A.A. , Prinsen Martine B.W. , de Man Jos , Buijsman Rogier C. , Uitdehaag Joost C.M.
Published: April 2023

Validation of CTNNB1 as a drug sensitivity biomarker for TTK inhibitors using isogenic cell lines
Supplemental Figure 6: UAB30 did not alter expression or phosphorylation of kinases. from Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies
Authors: Waters Alicia M. , Stewart Jerry E. , Atigadda Venkatram R. , Mroczek-Musulman Elizabeth , Muccio Donald D. , Grubbs Clinton J. , Beierle Elizabeth A.
Published: April 2023

The effects of UAB30 upon the expression and phosphorylation of kinases involved in cellular survival and apoptosis were evaluated with immunoblotting. Cells were treated with UAB30 (10 µM) and whole cell lysates were examined with immunoblotting for total and phosphorylated ERK1/2, total and phospho-FAK, total and phospho-SRC and total and phosphorylated AKT on SDS-PAGE gels. UAB30 did not result in an increase in kinase expression or phosphorylation in any of the cell lines studied. The phosphorylation of the kinases followed the expression of the total protein.
Figure S8 from Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-Cell Lymphoma
Authors: Jain Salvia , Washington Abigail , Leaf Rebecca Karp , Bhargava Parul , Clark Rachael A. , Kupper Thomas S. , Stroopinsky Dina , Pyzer Athalia , Cole Leandra , Nahas Myrna , Apel Arie , Rosenblatt Jacalyn , Arnason Jon , Kufe Donald , Avigan David
Published: April 2023

Decitabine and MUC1-C inhibitor combination increases hydrogen peroxide (H2O2) levels, which is abrogated by addition of NAC in primary CTCL cells
Figure S2 from Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-Cell Lymphoma
Authors: Jain Salvia , Washington Abigail , Leaf Rebecca Karp , Bhargava Parul , Clark Rachael A. , Kupper Thomas S. , Stroopinsky Dina , Pyzer Athalia , Cole Leandra , Nahas Myrna , Apel Arie , Rosenblatt Jacalyn , Arnason Jon , Kufe Donald , Avigan David
Published: April 2023

Decitabine and MUC1-C inhibitor combination increases hydrogen peroxide (H2O2) levels and is cytotoxic in Myla cells
Fig S1 from CD3-Bispecific Antibody Therapy Turns Solid Tumors into Inflammatory Sites but Does Not Install Protective Memory
Authors: Benonisson Hreinn , Altıntaş Işıl , Sluijter Marjolein , Verploegen Sandra , Labrijn Aran F. , Schuurhuis Danita H. , Houtkamp Mischa A. , Verbeek J. Sjef , Schuurman Janine , van Hall Thorbald
Published: April 2023

Sequence and quality of bsAb
Figure S3 from Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy and Improved Retinal Toxicity with Nicotinic Acid Coadministration
Authors: Zhao Genshi , Green Colin F. , Hui Yu-Hua , Prieto Lourdes , Shepard Robert , Dong Sucai , Wang Tao , Tan Bo , Gong Xueqian , Kays Lisa , Johnson Robert L. , Wu Wenjuan , Bhattachar Shobha , Del Prado Miriam , Gillig James R. , Fernandez Maria-Carmen , Roth Ken D. , Buchanan Sean , Kuo Ming-Shang , Geeganage Sandaruwan , Burkholder Timothy P.
Published: April 2023

Addition of NAM rescued the inhibitory activity of LSN3154567
Supp. Table 2 from Exportin 1 Inhibition Induces Nerve Growth Factor Receptor Expression to Inhibit the NF-κB Pathway in Preclinical Models of Pediatric High-Grade Glioma
Authors: DeSisto John A. , Flannery Patrick , Lemma Rakeb , Pathak Amrita , Mestnik Shelby , Philips Natalie , Bales Natalie J. , Kashyap Trinayan , Moroze Erin , Venkataraman Sujatha , Kung Andrew L. , Carter Bruce D. , Landesman Yosef , Vibhakar Rajeev , Green Adam L.
Published: April 2023

NCI approved anti-cancer agents in combination drug screen with selinexor
Supplementary Data from Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD
Authors: Zhao Liang , Chen Haojun , Guo Zhide , Fu Kaili , Yao Lanling , Fu Li , Guo Weixi , Wen Xuejun , Jacobson Orit , Zhang Xianzhong , Sun Long , Wu Hua , Lin Qin , Chen Xiaoyuan
Published: April 2023

Supplementary Data
Supplementary Table S2 from Targeting Phosphorylation of Y-Box–Binding Protein YBX1 by TAS0612 and Everolimus in Overcoming Antiestrogen Resistance
Authors: Shibata Tomohiro , Watari Kosuke , Kawahara Akihiko , Sudo Tomoya , Hattori Satoshi , Murakami Yuichi , Izumi Hiroto , Itou Junji , Toi Masakazu , Akiba Jun , Akagi Yoshito , Tanaka Maki , Kuwano Michihiko , Ono Mayumi
Published: April 2023

YBX1 and pYBX1 (S102) expression of 397 invasive breast cancer patients obtained from TCGA (Breast Invasive Carcinoma (TCGA, Provisional).
Supplementary Tables from The Discovery of SWI/SNF Chromatin Remodeling Activity as a Novel and Targetable Dependency in Uveal Melanoma
Authors: Rago Florencia , Elliott GiNell , Li Ailing , Sprouffske Kathleen , Kerr Grainne , Desplat Aurore , Abramowski Dorothee , Chen Julie T. , Farsidjani Ali , Xiang Kay X. , Bushold Geoffrey , Feng Yun , Shirley Matthew D. , Bric Anka , Vattay Anthony , Möbitz Henrik , Nakajima Katsumasa , Adair Christopher D. , Mathieu Simon , Ntaganda Rukundo , Smith Troy , Papillon Julien P.N. , Kauffmann Audrey , Ruddy David A. , Bhang Hyo-eun C. , Castelletti Deborah , Jagani Zainab
Published: April 2023

Supplementary Table S1 lists biochemical and cellular activity of BRG1/BRM inhibitors. Supplementary Table S2 lists BRM011 and BRM014 activity across cell line panel. Supplementary Table S3 lists cell lines generated for this study. Supplementary Table S4 lists antibody and qPCR probes used in this study.
Figure S3 from Circulating Tumor Cells and Biomarker Modulation with Olaratumab Monotherapy Followed by Olaratumab plus Doxorubicin: Phase Ib Study in Patients with Soft-Tissue Sarcoma
Authors: Martín-Broto Javier , Pousa Antonio López , Brohl Andrew S. , Van Tine Brian A. , Powers Benjamin , Stacchiotti Silvia , Blay Jean-Yves , Hu James S. , Oakley Gerard J. , Wang Hong , Szpurka Anna M. , Levy Donna E. , Mo Gary , Ceccarelli Matteo , Jones Robin L.
Published: April 2023

CTC enumeration patterns in all population CTCs by best overall response rate.
Supplementary Data from HJM-561, a Potent, Selective, and Orally Bioavailable EGFR PROTAC that Overcomes Osimertinib-Resistant EGFR Triple Mutations
Authors: Du Yong , Chen Yongfeng , Wang Yuxia , Chen Jinju , Lu Xiaorong , Zhang Li , Li Yan , Wang Zhaofu , Ye Guozhong , Zhang George
Published: April 2023

Supplementary Data from HJM-561, a Potent, Selective, and Orally Bioavailable EGFR PROTAC that Overcomes Osimertinib-Resistant EGFR Triple Mutations
Abstract 116: A novel murine model for interrogating tumor heterogeneity in non-small cell lung cancer
Authors: Oh Michael S. , Abascal Jensen W. , Tran Linh M. , Salehi-Rad Ramin , Lim Raymond J. , Kahangi Bitta P. , Crosson William P. , Reyes Edgar Perez , Yang Jacey , Yeah Cara , Krysan Kostyantyn , Liu Bin , Dubinett Steven M.
Published: April 2023

Treatment for non-small cell lung cancer (NSCLC) has been transformed by the use of immune checkpoint inhibitors (ICIs), which promote the ability of the immune system to attack cancer cells. Resistance to these therapies thus represents a major barrier to effectively treating patients with NSCLC. Tumor heterogeneity has been identified as an important factor that may mediate ICI resistance, and prior analyses of NSCLC tumors have accordingly shown that greater tumor heterogeneity is correlated with diminished response to ICIs. However, the exact mechanisms of heterogeneity-mediated resistance remain unclear, and there exist a lack of models for studying the impact of tumor heterogeneity on therapeutic efficacy in NSCLC. To address this issue, we have developed a novel murine model of NSCLC that incorporates a system of clonal cell lines to precisely modulate tumor heterogeneity. Specifically, we isolated single tumor cells from a murine NSCLC cell line harboring 3 common driver mutations (KrasG12DTp53+/−Lkb1−/−, or “KPL”). We additionally isolated single cells after mutagenizing the KPL line with the alkylating agent N-methyl-N-nitrosourea, in order to obtain clones that better reflect the higher tumor mutation burden often seen in NSCLC. Clonal cell lines were derived from these single cells and then analyzed using whole exome sequencing to verify clonality and characterize their mutational profile. Phylogenetic analysis of mutations yielded categorization of these clones into 5 clusters. Clones within the same cluster demonstrated comparable in vivo growth kinetics and similar response to anti-PD-1 immunotherapy. Combinations of these clones can be used to recapitulate various levels of heterogeneity and to form tumors with differing responses to PD-1 inhibition. Our results validate this system of clonal cell lines as a model of NSCLC that can modify multiple aspects of tumor heterogeneity and thus provide insights into the effects of tumor heterogeneity on ICIs and other immunotherapies.

Citation Format: Michael S. Oh, Jensen W. Abascal, Linh M. Tran, Ramin Salehi-Rad, Raymond J. Lim, Bitta P. Kahangi, William P. Crosson, Edgar Perez Reyes, Jacey Yang, Cara Yeah, Kostyantyn Krysan, Bin Liu, Steven M. Dubinett. A novel murine model for interrogating tumor heterogeneity in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 116.
Abstract 1226: SETD2 loss in renal epithelial cells induces epithelial to mesenchymal transition in a TGFβ-independent manner
Authors: Wang Tianchu , Wagner Ryan , Hlady Ryan , Kim Sungho , Pan Xiaoyu , Ho Thai , Robertson Keith
Published: April 2023

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC) and accounts for majority of the deaths from renal cancer. SETD2, the sole histone methyltransferase that catalyzes trimethylation of lysine 36 on histone H3 (H3K36me3), is frequently mutated in ccRCC. Studies have shown that SETD2 mutations are often subclonal and the mutation rate dramatically increases from 25% in primary ccRCC to more than 60% in metastatic ccRCC, suggesting SETD2 loss plays an important role in renal cancer metastasis. However, mechanisms underpinning how SETD2 mutation drives invasion and metastasis in ccRCC is largely unknown. Here, by performing RNA-seq and ATAC-seq in a non-tumorigenic renal epithelial cell line isogenic for SETD2 loss-of-function, we found that SETD2 inactivation induces dramatic changes in the transcriptome and drastically enhances chromatin accessibility, which allows binding of a variety of transcription factors. We also discovered that SETD2 loss induces a TGFβ-independent EMT program, which is a major pathway linked to metastasis. Correlation of RNA-seq with ATAC-seq identifies SOX2, OCT2 and PRRX1 as key transcription factors promoting the SETD2 loss-driven EMT program. Furthermore, we found that this distinct EMT program is in part triggered by secreted factors, which suggests that SETD2 mutation promotes a metastasis-permissive tumor microenvironment through paracrine signaling. In summary, our findings reveal that SETD2 is a key regulator of EMT phenotypes that may explain the role of SETD2 mutations in ccRCC metastasis and further uncover potential therapeutic targets for SETD2-mutant ccRCC patients.

Citation Format: Tianchu Wang, Ryan Wagner, Ryan Hlady, Sungho Kim, Xiaoyu Pan, Thai Ho, Keith Robertson. SETD2 loss in renal epithelial cells induces epithelial to mesenchymal transition in a TGFβ-independent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1226.
Abstract 1228: TCF1 orchestrates the epithelial/mesenchymal hybrid phenotype in basal breast cancer via upregulation of FOXC2 leading to stemness and metastasis
Authors: Liang Huizhi , Benard Outhiriaradjou , Suyama Kimita , Ren Zuen , Wang Hao , Norton Larry , Hazan Rachel
Published: April 2023

The epithelial to mesenchymal transition (EMT) is a dynamic process driven by carcinoma cells undergoing partial and/or complete EMT, leading to tumor heterogeneity and malignancy. Here we show that TCF1, a TCF7 gene product, promotes an epithelial/mesenchymal hybrid (E/M) phenotype that was enriched in canonical Wnt signaling, stemness and metastatic properties. TCF1 knockdown in PyMT mammary tumor cells suppressed stemness and metastasis coincident with attenuation of the E/M phenotype in vivo. Interestingly, E/M cells (CD104highCD44high) isolated from human basal-like breast cancer cell lines, were enriched in TCF1, EMT and stemness markers relative to M cells (CD104 lowCD44high). In vivo, E/M cells showed dramatically increased tumorigenic, metastatic and organoid-forming potential as compared to M cells; which were in turn provoked by TCF1 overexpression in bulk mammary cancer cells. Remarkably, RNA sequencing unraveled striking upregulation of FOXC2 in E/M relative to M cells, which was suppressed by TCF1 inhibition. Moreover, FOXC2 knockdown in E/M cells destabilized the E/M state, whereas FOXC2 overexpression induced M to E/M transition. Together, these results demonstrate that TCF1 orchestrates the E/M state via upregulation of FOXC2, resulting in stemness and metastasis.

Citation Format: Huizhi Liang, Outhiriaradjou Benard, Kimita Suyama, Zuen Ren, Hao Wang, Larry Norton, Rachel Hazan. TCF1 orchestrates the epithelial/mesenchymal hybrid phenotype in basal breast cancer via upregulation of FOXC2 leading to stemness and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1228.
Abstract 1229: Deciphering molecular mechanisms of metastasis in renal cell carcinoma
Authors: Arner Emily Nicole , Wolf Melissa M. , Vlach Logan , Sih Vania J. , Greenwood Dalton L. , Haake Scott , Rathmell Jeffrey C. , Rathmell Kimryn
Published: April 2023

Across human cancer, tumors that are high grade, poorly differentiated, and have undergone epithelial-to-mesenchymal transition (EMT) carry a worse prognosis with a high likelihood of metastasizing to distant organs. Despite significant research efforts, metastatic cancers and relapse remain the primary cause of cancer related deaths. In renal cell carcinoma (RCC), metastasis is present in one-third of patients at the time of diagnosis, and one-third of patients who initially present with locally advanced disease eventually develop local or distant recurrence following resection of the primary tumor, highlighting the need for new RCC therapies and further insight into the metastatic process. Using patient biopsies, immunohistochemistry, sequencing, and available clinical data in a cohort of RCC patients, we found that patients with more epithelial tumors have a significantly lower risk of recurrence. Unexpectedly, patients whose tumors had a mesenchymal protein signature had significantly increased infiltration of macrophages within their tumors. Additionally, increased macrophages in the primary tumor were significantly associated with a higher tumor stage at diagnosis and worse overall survival, suggesting that macrophages may play an important role in EMT in ccRCC. Furthermore, whole exome sequencing revealed that patients with increased macrophage infiltrate had a mutational loss of SETD2, a histone methyltransferase. Additionally, macrophages and EMT are also correlated, and tumor cell adhesion is reduced when SETD2 is lost in ccRCC patients. Further studies are needed to determine if SETD2 loss plays a role in the recruitment of macrophages to the tumor and EMT. Further characterization of the gene signatures, metabolic phenotypes, and immune cell infiltrate within these patient samples will lead to a better understanding of metastasis in an oncogene- and tissue-specific manner and thus lead to more efficacious therapies for metastatic patients.

Citation Format: Emily Nicole Arner, Melissa M. Wolf, Logan Vlach, Vania J. Sih, Dalton L. Greenwood, Scott Haake, Jeffrey C. Rathmell, Kimryn Rathmell. Deciphering molecular mechanisms of metastasis in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1229.
Abstract 1296: Targeting nuclear AURKA and hypoxia signaling pathway attenuates metastatic burden in triple negative breast cancer
Authors: Maskey Abha , Whately Kristina Marinak , Pugacheva Elena N.
Published: April 2023

Despite remarkable progress in diagnosis and treatment, metastasis from the primary tumor to distant organs is responsible for over 90% of cancer deaths. Therefore, there is a need to understand the drivers of the process to detect, target, and develop therapeutics to treat metastases better and extend their lifespan. Aurora-A Kinase (AURKA) is a serine/threonine kinase that typically localizes in the cytoplasm. However, the nuclear localization of AURKA (N-AURKA) has been reported in multiple cancers and correlates with poor survival and the advanced/metastatic stage of the disease. AURKA is often present in the nucleus of metastatic Triple Negative Breast Cancer (TNBC) cells and patient biopsies compared to non-metastatic cells. Moreover, induced translocation of AURKA to the nucleus in experimental models of TNBC results in a 5-fold increase in metastases to the bones, lungs, and liver compared to AURKA in the cytoplasm. We have previously shown that N-AURKA under normoxic conditions binds to HIF1A/1B and leads to induction of hypoxia signaling via transactivation of Hypoxia Inducible Factors (HIFs)-dependent genes, including migration/invasion, survival/death, and stemness, promoting early cancer dissemination. Transactivation of HIF1-genes requires cofactor p300/CBP. It is currently unknown if N-AURKA/HIF1 transcription is p300 dependent. In this study, we used the small molecular inhibitor Chetomin to disrupt the interaction of HIF1A and co-activator CBP/p300 in experimental TNBC and animal models combined with AURKA inhibitor Alisertib. Disruption of the hypoxia signaling pathway significantly decreases the transactivation of HIF-dependent genes, including migration/invasion, survival/death, and stemness in N-AURKA cells. Moreover, in mouse models, inhibition of HIF1 activity via treatment with Chetomin in combination with AURKA inhibitor Alisertib significantly decreased metastatic burden suggesting that p300 binding to AURKA/HIF complex is critical for gene expression and enabling metastatic dissemination/colonization. Our studies show the mechanistic relationship between N-AURKA and hypoxia signaling and lay the foundation for developing novel combination treatment strategies to improve patient outcomes.

Citation Format: Abha Maskey, Kristina Marinak Whately, Elena N. Pugacheva. Targeting nuclear AURKA and hypoxia signaling pathway attenuates metastatic burden in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1296.
Abstract 1354: Proteasome activation prevents T cell exhaustion and improves antitumor activity
Authors: de Blas Ander , Andreatta Massimo , Antoñana-Vildosola Asier , Velasco Paloma , Egia-Mendikute Leire , Jimenez-Lasheras Borja , Zanetti Samanta Romina , Carmona Santiago J. , Prieto-Fernández Endika , Palazon Asis
Published: April 2023

Tumor infiltrating lymphocytes (TILs) exert their antitumor activity in the tumor microenvironment (TME). Chronic TCR stimulation, together with features of the tumor microenvironment such as hypoxia, result in T cell exhaustion. Exhausted T cells (TEX) are characterized by oxidative stress that leads to cellular accumulation of oxidized proteins. Because the proteasome complex clears oxidized proteins, we hypothesized that its capacity might be overloaded in TEX, limiting their fitness.

Analysis of single-cell transcriptomics data from 19 tumor types indicated an increased proteasome activity in TEX compared to non-exhausted TILs. Higher levels of ROS-induced protein oxidation, expression of proteasome genes and proteasome activity were confirmed in human TEX, suggesting that increased proteasome activity might be a compensatory mechanism to exhaustion-associated oxidative stress. We show that pharmacological activation of the proteasome prevented T cell exhaustion, and lead to superior anti-tumor control in the context of adoptive cell therapy in mouse models. Thus, modulation of the proteasome activity is an attractive strategy to prevent T cell dysfunction promoted by the TME, and to potentially overcome this major obstacle in cancer immunotherapies against solid tumors.

Citation Format: Ander de Blas, Massimo Andreatta, Asier Antoñana-Vildosola, Paloma Velasco, Leire Egia-Mendikute, Borja Jimenez-Lasheras, Samanta Romina Zanetti, Santiago J. Carmona, Endika Prieto-Fernández, Asis Palazon. Proteasome activation prevents T cell exhaustion and improves antitumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1354.
Abstract 1356: The tumor immune microenvironment of recurrent nasopharyngeal carcinoma
Authors: Ma Jingyi , James Anne , Poh Jolene , Chua Magdalene Jahn May , Poh Qianhui , Alsagoff Sharifah Azzah Binte Syed Mohamad Anis , Sam Xinxiu , Tan Geksan , Lim Chekang , Selvarajan Sathiyamoorthy , Lim Tony Kiat Hon , Mong Jamie Chen Yee , Lim Chweeming
Published: April 2023

Nasopharyngeal carcinoma (NPC) is endemic in southern China and Southeast Asia. While primary tumors respond well to radiotherapy with or without chemotherapy, the management of recurrent/metastatic (RM) diseases is a challenge. What contributes to the refractoriness of RM NPC remains to be elucidated. In this study, we recruited patients who developed local recurrences or distal metastases. Gene expression profiles of tumor cells, tumor stroma and tumor-infiltrating immune cells in paired primary and RM NPC samples were obtained by targeted mRNA sequencing techniques. It was found that RM NPC, compared to their primary compartment, showed significant enrichment of immune cell-related gene signatures. This was associated with an altered immune cell composition, with enhanced T cell activation and exhaustion coupled with an M2-skewed macrophage population. Together, these data depict a more inflamed yet immunosuppressive microenvironment of RM NPC and highlight macrophages being a potential target to reinvigorate antitumoral immune responses.

Citation Format: Jingyi Ma, Anne James, Jolene Poh, Magdalene Jahn May Chua, Qianhui Poh, Sharifah Azzah Binte Syed Mohamad Anis Alsagoff, Xinxiu Sam, Geksan Tan, Chekang Lim, Sathiyamoorthy Selvarajan, Tony Kiat Hon Lim, Jamie Chen Yee Mong, Chweeming Lim. The tumor immune microenvironment of recurrent nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1356.
Abstract 1431: Sprouty 2 expression attenuates proliferation in nras-driven acute myeloid leukemia cell lines
Authors: Roberts Michael , Bahadur Sher , Albitz Coltin , Chung Jae , Garcia Samantha , Nguyen Cuong , Kovatsis Sophia
Published: April 2023

Oncogenic mutations in the NRAS gene are found in many cancers including a subset of acute myeloid leukemias (AML). Established AML cell lines exhibiting hyperactive signaling through the RAS-RAF-MEK-ERK pathway show constitutive ERK activation generating a transcriptome that mediates escape from programmed cell death and continuous proliferation. It has been established that exposure of many AML cell lines to phorbol esters such as phorbol-12-myristate-13-acetate (PMA) mediates cell cycle arrest, myeloid differentiation, and apoptosis. This effect seems counterintuitive given that PMA irreversibly activates protein kinase C (PKC), which enhances ERK activity leading to transcriptional upregulation of target genes controlled by ERK activated transcription factors, many of which promote proliferation. Here we define a set of PMA response genes in AML cell lines driven by oncogenic NRAS that encode negative regulators of RAS-RAF-MEK-ERK signaling, including SPRY2, RASA1, DUSP 5, and DUSP6. Additionally, we show that overexpression of SPRY2 alone attenuates proliferation by inhibiting ERK activation and altering the AML cell transcriptome through the activation of genes encoding members of the AP-1 transcription factor family, FOS, JUNB, and JUND, and the cyclin-CDK inhibitors CDKN1A and CDKN2B. We hypothesize that oncogenic NRAS signaling is overridden by PMA treatment through the activation of ERK target genes that ultimately inhibit the MAPK-ERK pathway, such as SPRY2. Finally, we show that SPRY 2 expression in AML patient samples represents a survival prognostic indicator where higher expression levels correlate with improved overall survival.

Citation Format: Michael Roberts, Sher Bahadur, Coltin Albitz, Jae Chung, Samantha Garcia, Cuong Nguyen, Sophia Kovatsis. Sprouty 2 expression attenuates proliferation in nras-driven acute myeloid leukemia cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1431.
Abstract 1454: SMAD3 promotes expression and activity of the androgen receptor in prostate cancer
Authors: Jeon Hee-Young , Pornour Majid , Ryu Hyunju , Khadka Sudeep , Xu Rui , Jang Jihyun , Li Deqiang , Chen Hegang , Hussain Arif , Fazli Ladan , Gleave Martin , Dong Xuesen , Wang Qianben , Barbieri Christopher , Qi Jianfei
Published: April 2023

Overexpression of the androgen receptor (AR) is the primary cause of development of castration-resistant prostate cancer (CRPC), although mechanisms upregulating AR transcription in this context are not well understood. Our RNA-seq analysis revealed AR as the top pathway altered after SMAD3 knockdown in prostate cancer cells. SMAD3 knockdown decreased levels of AR, AR-V7 and AR target gene transcripts, whereas SMAD4 or SMAD2 knockdown had little or no effect. ChIP-seq analysis showed that SMAD3 knockdown decreased global binding of AR to chromatin. Mechanistically, we show that SMAD3 binds to intron 3 of the AR gene to promote AR expression. Targeting these binding sites by CRISPRi reduced transcript levels of AR and AR targets. In addition, ~50% of AR or SMAD3 ChIP-seq peaks overlapped, and SMAD3 may also cooperate with or co-activate AR in terms of AR target expression. Functionally, AR re-expression in SMAD3-knockdown cells partially rescued AR target expression and cell growth defects. AR and SMAD3 mRNAs were upregulated in datasets of metastatic prostate cancer and CRPC compared with primary prostate cancer. This study suggests that SMAD3 could be targeted to downregulate AR expression and activity and as potential anti-prostate cancer therapy.

Citation Format: Hee-Young Jeon, Majid Pornour, Hyunju Ryu, Sudeep Khadka, Rui Xu, Jihyun Jang, Deqiang Li, Hegang Chen, Arif Hussain, Ladan Fazli, Martin Gleave, Xuesen Dong, Qianben Wang, Christopher Barbieri, Jianfei Qi. SMAD3 promotes expression and activity of the androgen receptor in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1454.
Abstract 1458: The PAX5 transcription factor is a suppressor of NFAT-mediated breast cancer aggressivity
Authors: Després Félix , Robichaud Damien , Hannay Brandon , Robichaud Gilles A.
Published: April 2023

Breast cancer metastasis is responsible for 90% of deaths associated with the disease. The understanding of mechanisms driving metastasis is thus vital to mitigate mortality rates and improve patient outcome. One of these mechanisms essential for breast cancer malignancy is the activation of the Nuclear Factor of Activated T cells (NFAT) pathway. Recently, we have reported that the PAX5 transcription factor induces breast cancer cell epithelialization, which in turn extinguishes mesenchymal transitioning, malignant features, and tumor progression. Our preliminary findings also suggests that PAX5 may negatively regulate NFAT-dependant pathways to modulate breast processes and potentially disease progression. We therefore hypothesized that PAX5 suppressed breast cancer malignancy through the targeted inhibition of the pro-malignant NFAT pathway. Using breast cancer cell models, we conditionally modulated PAX5 levels by transfection and recombinant expression to characterize PAX5-induced inhibition of the NFAT activation pathway and its mechanisms of action. Technically, expression levels for NFAT members (1 to 5) and their regulators (ex: calcium mobilization, specific kinases, and phosphatases) were assessed using RT-qPCR and Western blotting. NFAT activation was also studied through the analysis of cellular compartmentalization, reporter gene assays, and microscopy. We observed that PAX5 suppressed overall NFAT-dependant transcriptional activity in breast cancer cells through various mechanisms depending on the type of breast cancer models. We also found that although elevated PAX5 expression levels do not alter total NFAT protein levels, PAX5 affects the phosphorylation status of NFAT (activation) through the regulation of NFAT-specific phosphatases and kinases controlling NFAT import and downstream transactivation pro-malignant genes. We also found that PAX5 modulates intracellular calcium mobilization, which is also essential for NFAT activation. Altogether, our findings demonstrate that PAX5 is a potent inhibitor of NFAT-dependant processes essential for in breast cancer malignancy. Interestingly, PAX5-mediated suppression of the NFAT pathway in breast cancer cells is elicited by multiple regulatory mechanisms, which also depend on breast cancer cell type. These studies provide new insight into the molecular pathways governing breast malignancy and disease progression. Further understanding of these mechanisms of action will build the future roadmaps for therapeutic and prognostic interventions.

Citation Format: Félix Després, Damien Robichaud, Brandon Hannay, Gilles A. Robichaud. The PAX5 transcription factor is a suppressor of NFAT-mediated breast cancer aggressivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1458.