tbuckley/cabot-search huggingface dataset:
Retrospective Real-Life Comparison of Obinutuzumab Plus Chlorambucil Versus Ibrutinib in Previously Untreated and Unfit Patients with Chronic Lymphocytic Leukemia without TP53 Disruptions. Interim Results from the Italian CLL Campus
Authors: Andrea Visentin, Francesca Romana Mauro, Daniela Pietrasanta, Alberto Fresa, Candida Vitale, Stefania Ciolli, Ramona Cassin, Francesca Cibien, Paolo Sportoletti, Massimo Gentile, Gian Matteo Rigolin, Francesca M. Quaglia, Roberta Murru, Alessandro Gozzetti, Stefano Molica, Monia Marchetti, Lydia Scarfo, Gianluigi Reda, Marta Coscia, Luca Laurenti, Giovanni Pizzolo, Gianpietro Semenzato, Robin Foà, Antonio Cuneo, Livio Trentin
Journal: Blood (2020)
XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53
Authors: Manman Deng, Mingzhi Zhang, Zijun Y. Xu-Monette, Lan V. Pham, Alexandar Tzankov, Carlo Visco, Xiaosheng Fang, Govind Bhagat, Feng Zhu, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D. Hsi, William W. L. Choi, Jooryung Huh, Maurilio Ponzoni, Andrés J. M. Ferreri, Michael B. Møller, Benjamin M. Parsons, J. Han van Krieken, Miguel A. Piris, Jane N. Winter, Fredrick Hagemeister, Lapo Alinari, Yong Li, Michael Andreeff, Bing Xu, Ken H. Young
Journal: Journal of Hematology & Oncology (2020)

The XPO1 inhibitor selinexor was recently approved in relapsed/refractory DLBCL patients but only demonstrated modest anti-DLBCL efficacy, prompting us to investigate the prognostic effect of XPO1 in DLBCL patients and the rational combination therapies in high-risk DLBCL. High XPO1 expression (XPO1high) showed significant adverse prognostic impact in 544 studied DLBCL patients, especially in those with BCL2 overexpression. Therapeutic study in 30 DLBCL cell lines with various molecular and genetic background found robust cytotoxicity of selinexor, especially in cells with BCL2-rearranged (BCL2-R+) DLBCL or high-grade B-cell lymphoma with MYC/BCL2 double-hit (HGBCL-DH). However, expression of mutant (Mut) p53 significantly reduced the cytotoxicity of selinexor in overall cell lines and the BCL2-R and HGBCL-DH subsets, consistent with the favorable impact of XPO1high observed in Mut-p53-expressing patients. The therapeutic effect of selinexor in HGBCL-DH cells was significantly enhanced when combined with a BET inhibitor INCB057643, overcoming the drug resistance in Mut-p53-expressing cells. Collectively, these data suggest that XPO1 worsens the survival of DLBCL patients with unfavorable prognostic factors such as BCL2 overexpression and double-hit, in line with the higher efficacy of selinexor demonstrated in BCL2-R+ DLBCL and HGBCL-DH cell lines. Expression of Mut-p53 confers resistance to selinexor treatment, which can be overcome by combined INCB057643 treatment in HGBCL-DH cells. This study provides insight into the XPO1 significance and selinexor efficacy in DLBCL, important for developing combination therapy for relapsed/refractory DLBCL and HGBCL-DH.
Phase I/II Dose-Escalation Study of Lenalidomide in Combination with R-GDP for Treatment of Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Followed By Maintenance Lenalidomide
Authors: Colin Phipps, Chandramouli Nagarajan, Lawrence Ng, Jane L Chua, Yunxin Chen, Shin Yeu Ong, Melinda Si Yun Tan, Nicholas Francis Grigoropoulos, Sathish Gopalakrishnan, Heng Joo Ng, William YK Hwang, Yeow Tee Goh, Yuh Shan Lee
Journal: Blood (2020)
Clinical Significance of Emergent Leukocytosis in Patients with Myelofibrosis Receiving JAK Inhibitor Therapy
Authors: Radovan Vasic, Yuliang Shi, Andrea Arruda, Sarah Malik, Jaime Claudio, Jose-Mario Capo-Chichi, Aniket Bankar, Hassan Sibai, Dawn Maze, James A. Kennedy, Wei Xu, Vikas Gupta
Journal: Blood (2020)
Pre-Clinical Validation of a Novel Erk1/2 and CDK4/6 Inhibitor Combination in Multiple Myeloma (MM)
Authors: Sophia Adamia, Shruti Bhatt, Yu-Tzu Tai, Kenneth Wen, Catherine A Nicholas, Marissa S Pioso, Ivane Abiatari, Anthony G. Letai, Kenneth Anderson
Journal: Blood (2020)
Treosulfan- Versus Melphalan-Based Reduced Intensity Conditioning in Sequential HLA-Haploidentical Transplantation Using Ptcy As GvHD Prophylaxis in High-Risk MDS /AML of the Elderly: A Matched-Pair Analysis
Authors: Alessia Fraccaroli, Sarah Haebe, Heidrun Drolle, Elena Stauffer, Veit Buecklein, Dusan Prevalsek, Michael von Bergwelt, Johanna Tischer
Journal: Blood (2020)
Pomalidomide, Dexamethasone, and Daratumumab after Lenalidomide Treatment in Relapsed Refractory Multiple Myeloma: Updated Results from an Open-Label, Multicenter, Phase 2 Trial
Authors: David S. Siegel, Gary J. Schiller, Christy J. Samaras, Michael Sebag, Jesus G. Berdeja, Siddhartha Ganguly, Jeffrey V. Matous, Kevin W Song, Christopher S. Seet, Mirelis Acosta-Rivera, Michael Bar, Donald P. Quick, Bertrand M. Anz, Gustavo A. Fonseca, Donna E. Reece, Kim Lee, Weiyuan Chung, Amit Agarwal, Nizar J. Bahlis
Journal: Blood (2020)
A Phase 2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of Cfi-400945 As a Single Agent or in Combination with Azacitidine or Decitabine in Patients with Acute Myeloid Leukemia
Authors: Brian A Jonas, Dale L. Bixby, Joseph M Brandwein, Karen W.L. Yee, Tracy Murphy, Mark D. Minden, Glenn C. Michelson, Mark R Bray, Emily Elizabeth Roberts-Thomson, Gautam Borthakur
Journal: Blood (2020)
Validation of a Predictive Score of Acute Chest Syndrome (presev-2 study) in Adults
Authors: Christian Kassasseya, Kene Sekou, Tatiana Besse-Hammer, Ruben Nzouakou, Jean-Benoît Arlet, Jean Magnang, Louis Affo, Sandrine Dautheville, Stéphanie Ngo, Mehdi Khellaf, Dapa Aly Diallo, Pablo Bartolucci
Journal: Blood (2020)
Use of Medium Potency Statins Is Associated with Improved Outcomes after Frontline RCHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Sushanth Gouni, Paolo Strati, Jason Westin, Loretta J. Nastoupil, Raphael E Steiner, Ranjit Nair, Luis Fayad, Sattva S. Neelapu, Ralf Landgraf, Daniel Bilbao, Francisco Vega, Nitin Agarwal
Journal: Blood (2020)
A Phase I Study of Selinexor and R-ICE in Patients with Relapsed/Refractory Aggressive B-Cell Lymphomas
Authors: Sarah C. Rutherford, John N. Allan, Jia Ruan, Richard R. Furman, Kristy Richards, Amelyn Rodriguez, Kseniya Gololobova, Arcania Garcia, Leandro Cerchietti, Rossella Marullo, Zhengming Chen, Jennifer Santamala, Tsiporah B. Shore, Adrienne A. Phillips, Sebastian Mayer, Jingmei Hsu, Usama Gergis, Silvia Senese, Trisha Ali-Shaw, Riyaad Rahim, Koen van Besien, John P. Leonard, Peter Martin
Journal: Blood (2020)
Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Sarah J. Schrauben, Haochang Shou, Xiaoming Zhang, Amanda Hyre Anderson, Joseph V. Bonventre, Jing Chen, Steven Coca, Susan L. Furth, Jason H. Greenberg, Orlando M. Gutierrez, Joachim H. Ix, James P. Lash, Chirag R. Parikh, Casey M. Rebholz, Venkata Sabbisetti, Mark J. Sarnak, Michael G. Shlipak, Sushrut S. Waikar, Paul L. Kimmel, Ramachandran S. Vasan, Harold I. Feldman, Jeffrey R. Schelling
Journal: Journal of the American Society of Nephrology (2020)

Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals.In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change.Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline.Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.
Anti-Tumor Activity of ASTX029, a Dual Mechanism Inhibitor of ERK1/2, in Preclinical AML Models
Authors: Christopher J. Hindley, Lynsey Fazal, Joanne M. Munck, Vanessa Martins, Alpesh D. Shah, Nicola E. Wilsher, Nicola G. Wallis, Harold N. Keer, John F. Lyons
Journal: Blood (2020)
Impact of Pre-Transplant Induction Therapy on Outcomes of Patients Who Undergo Autologous Stem Cell Transplantation for Mantle Cell Lymphoma in First Complete Remission
Authors: Omar Albanyan, Samer Alkassis, Seongho Kim, Andrew Kin, Asif Alavi, Lois Ayash, Voravit Ratanatharathorn, Dipenkumar Modi, Joseph P. Uberti, Abhinav Deol
Journal: Blood (2020)
Multiple Myeloma Cell Defects Erythropoiesis and Results Anemia Via High Level of CCL3 in Bone Marrow Microenvironment
Authors: Lanting Liu, Zhen Yu, Hui Cheng, Weiwei Sui, Shuhui Deng, Xiaojing Wei, Chenxing Du, Wenyang Huang, Gang An, Wen Zhou, Tao Cheng, Lugui Qiu, Mu Hao
Journal: Blood (2020)
Abstract 378: Physiologic Role of <i>Rpl13a</i> SnoRNAs in Cell Size Regulation
Authors: Hsiang Ting T Ho, Christopher L Holley
Journal: Circulation Research (2020)

Objectives: Box C/D small nucleolar RNAs (snoRNA) are a multifunctional family of ncRNAs that play a critical role in guiding 2'- O -methylation (Nm) of ribosomal RNA (rRNA). My work has recently revealed that box C/D snoRNAs can also direct methylation of messenger RNA (mRNA), and that this methylation can regulate mRNA translation in the heart. In studies of genetically-engineered mice lacking four box C/D snoRNAs, I have observed that the knockout animals have relatively small hearts compared to wild-type. The objective of my current study is to define the specific mechanisms by which box C/D snoRNAs regulate heart size. Methods: I investigated the hearts of genetically-engineered mice lacking four box C/D snoRNAs from the Rpl13a locus (snoRNAs U32a, U33, U34 and U35a ). I also used antisense oligonucleotides to knock down these snoRNAs in H9c2 rat cardiomyoblasts. Changes in gene and protein expression were assessed by qPCR and immunoblot. Relative Nm modification of mRNA was determined by reverse transcription at low dNTP concentrations, followed by real-time PCR (RTL-P). Results: Germline knockout of the four box C/D Rpl13a snoRNAs ( U32a, U33, U34 and U35a ) in adolescent mice produces developmentally smaller hearts. In H9c2 rat cardiomyoblasts, knockdown of Rpl13a snoRNAs by antisense oligonucleotides significantly reduces H9c2 cell size. These concordant effects on organ and cell size suggest that the Rpl13a snoRNAs might be regulating critical pathways that determine cell growth. Using a candidate gene approach, I found that Mtor mRNA and protein expression is significantly reduced in hearts from Rpl13a snoRNA knockout mice. Preliminary results using the RTL-P method suggest that Mtor is subject to snoRNA-guided Nm modification, which is decreased in Rpl13a snoRNA knockout mouse hearts. Conclusion: These results suggest that Rpl13a snoRNAs regulate cardiomyocyte growth, at least in part, by guiding Nm modification of Mtor mRNA.
Progenitor cell-derived exosomes endowed with VEGF plasmids enhance osteogenic induction and vascular remodeling in large segmental bone defects
Authors: Yao Zha, Yawu Li, Tianyi Lin, Jia Chen, Shengmin Zhang, Jianglin Wang
Journal: Theranostics (2020)

Large segmental bone regeneration remains a great challenge due to the lack of vascularization in newly formed bone. Conventional strategies primarily combine bone scaffolds with seed cells and growth factors to modulate osteogenesis and angiogenesis. Nevertheless, cell-based therapies have some intrinsic issues regarding immunogenicity, tumorigenesis, bioactivity and off-the-shelf transplantation. Exosomes are nano-sized (50-200 nm) extracellular vesicles with a complex composition of proteins, nucleic acids and lipids, which are attractive as therapeutic nanoparticles for disease treatment. Exosomes also have huge potential as desirable drug/gene delivery vectors in the field of regenerative medicine due to their excellent biocompatibility and efficient cellular internalization. Methods: We developed a cell-free tissue engineering system using functional exosomes in place of seed cells. Gene-activated engineered exosomes were constructed by using ATDC5-derived exosomes to encapsulate the VEGF gene. The specific exosomal anchor peptide CP05 acted as a flexible linker and effectively combined the engineered exosome nanoparticles with 3D-printed porous bone scaffolds. Results: Our findings demonstrated that engineered exosomes play dual roles as an osteogenic matrix to induce the osteogenic differentiation of mesenchymal stem cells and as a gene vector to controllably release the VEGF gene to remodel the vascular system. In vivo evaluation further verified that the engineered exosome-mediated bone scaffolds could effectively induce the bulk of vascularized bone regeneration. Conclusion: In our current work, we designed specifically engineered exosomes based on the requirements of vascularized bone repair in segmental bone defects. This work simultaneously illuminates the potential of functional exosomes in acellular tissue engineering.
Loss of Alpha Globin Genes in Human Subjects Is Associated with Improved Nitric Oxide-Mediated Vascular Perfusion
Authors: Christopher C Denton, Payal Shah, Silvie Suriany, Honglei Liu, Wanwara Thuptimdang, John Sunwoo, Patjanaporn Chalacheva, Saranya Veluswamy, Roberta Miyeko Kato, John C Wood, Jon A Detterich, Michael C.K. Khoo, Thomas D. Coates
Journal: Blood (2020)
Identification of Prognostic Immunophenotypes at First Diagnosis in Patients with Acute Myeloid Leukemia (AML) By a Standardized Multicolor Flow Cytometry (MFC) Panel Originally Designed to Detect Measurable Residual Disease (MRD) at Follow-up
Authors: Maximilian Alexander A Rohnert, Malte von Bonin, Michael Kramer, Philipp Ensel, Nadja Holtschke, Christoph Rollig, Martin Bornhäuser, Veit Buecklein, Marion Subklewe, Stefan W Krause, Simon Voelkl, Tobias Berg, Michael A Rieger, Cornelia Brendel, Jörg Hoffmann, Nicole Hofmeister-Mielke, Richard F. Schlenk, Sylvie D Freeman, Uta Oelschlägel
Journal: Blood (2020)
A Systematic Review of Daratumumab Based Four Drug Regimen for Newly Diagnosed Multiple Myeloma in Phase III Clinical Trials
Authors: Karun Neupane, Zahoor Ahmed, Amna Khan, Rabia Ashraf, Moazzam Shahzad, Shaha Nabeel, Arshia Akbar, Saad Javed, Syed Maaz Abdullah, Unaiza Faizan, Faiz Anwer
Journal: Blood (2020)
Recent Advances in Electrical Neural Interface Engineering: Minimal Invasiveness, Longevity, and Scalability
Authors: Lan Luan, Jacob T. Robinson, Behnaam Aazhang, Taiyun Chi, Kaiyuan Yang, Xue Li, Haad Rathore, Amanda Singer, Sudha Yellapantula, Yingying Fan, Zhanghao Yu, Chong Xie
Journal: Neuron (2020)
Letter to the editor: prediction of survival in colorectal cancer using artificial intelligence
Authors: Ai Guan, Lejia Sun, Meixi Liu, Yilei Mao
Journal: Gut (2020)

We have read with great interest the article published in Gut by Bibault et al .1 The authors carried out a retrospective study including 154 900 patients from the prostate, lung colorectal and ovarian cancer screening trial to comprehensively train and validate a model to predict survival in colorectal cancer (CRC), using a gradient-boosted machine (GBM). Bibault et al 1 found that physical activity, T stage and tumour grade were the three most critical features among all relevant features. The study showed that the developed model has significant predictive power for survival in patients with CRC. We appreciate their efforts to provide insights into the survival prediction of patients with CRC. However, some points are worthy of further discussion.

First, the essential prognostic factors of patients with CRC, including lymphovascular …
<i>SF3B1</i>-Mutant Myelodysplastic Syndrome with Ringed Sideroblasts (MDS-RS) at the Single-Cell Level
Authors: Rashmi Kanagal-Shamanna, Vera Adema, Feiyang Ma, Andrea Santoni, Hui Yang, Irene Ganan-Gomez, Natthakan Thongon, Guillermo Montalban-Bravo, Matteo Pellegrini, Carlos E. Bueso-Ramos, Guillermo Garcia-Manero, Simona Colla
Journal: Blood (2020)
CD58 Aberrations Limit Durable Responses to CD19 CAR in Large B Cell Lymphoma Patients Treated with Axicabtagene Ciloleucel but Can be Overcome through Novel CAR Engineering
Authors: Robbie G. Majzner, Matthew J. Frank, Christopher Mount, Aidan Tousley, David M. Kurtz, Brian Sworder, Katherine A Murphy, Antigoni Manousopoulou, Kennedy Kohler, Maria Caterina Rotiroti, Jay Y. Spiegel, Yasodha Natkunam, Sheren F. Younes, Elena Sotillo, Vandon Duong, Charles Macaulay, Zinaida Good, Peng Xu, Louai Labanieh, Leo D Wang, Ash A. Alizadeh, Michelle Monje, David B. Miklos, Crystal L. Mackall
Journal: Blood (2020)
Different Subsets of Haematopoietic Cells and Immune Cells in Bone Marrow between Young and Old Donors
Authors: Weili Yao, Qi Wen, Hong-Yan Zhao, Yuan-Yuan Zhang, Shuqian Tang, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao Jun Huang, Yuan Kong
Journal: Blood (2020)
Implantation of regenerative complexes in traumatic brain injury canine models enhances the reconstruction of neural networks and motor function recovery
Authors: Jipeng Jiang, Chen Dai, Xiaoyin Liu, Lujia Dai, Ruixin Li, Ke Ma, Huiyou Xu, Fei Zhao, Zhiwen Zhang, Tao He, Xuegang Niu, Xuyi Chen, Sai Zhang
Journal: Theranostics (2020)

Rationale: The combination of medical and tissue engineering in neural regeneration studies is a promising field. Collagen, silk fibroin and seed cells are suitable options and have been widely used in the repair of spinal cord injury. In this study, we aimed to determine whether the implantation of a complex fabricated with collagen/silk fibroin (SF) and the human umbilical cord mesenchymal stem cells (hUCMSCs) can promote cerebral cortex repair and motor functional recovery in a canine model of traumatic brain injury (TBI). Methods: A porous scaffold was fabricated with cross-linked collagen and SF. Its physical properties and degeneration rate were measured. The scaffolds were co-cultured with hUCMSCs after which an implantable complex was formed. After complex implantation to a canine model of TBI, the motor evoked potential (MEP) and magnetic resonance imaging (MRI) were used to evaluate the integrity of the cerebral cortex. The neurologic score, motion capture, surface electromyography (sEMG), and vertical ground reaction force (vGRF) were measured in the analysis of motor functions. In vitro analysis of inflammation levels was performed by Elisa while immunohistochemistry was used in track the fate of hUCMSCs. In situ hybridization, transmission electron microscope, and immunofluorescence were used to assess neural and vascular regeneration. Results: Favorable physical properties, suitable degradation rate, and biocompatibility were observed in the collagen/SF scaffolds. The group with complex implantation exhibited the best cerebral cortex integrity and motor functions. The implantation also led to the regeneration of more blood vessels and nerve fibers, less glial fibers, and inflammatory factors. Conclusion: Implantation of this complex enhanced therapy in traumatic brain injury (TBI) through structural repair and functional recovery. These effects exhibit the translational prospects for the clinical application of this complex.
Impact of COVID-19 on maternal and neonatal outcomes: a systematic review and meta-analysis
Authors: Francesca Di Toro, Mattheus Gjoka, Giovanni Di Lorenzo, Davide De Santo, Francesco De Seta, Gianpaolo Maso, Francesco Maria Risso, Federico Romano, Uri Wiesenfeld, Roberto Levi-D'Ancona, Luca Ronfani, Giuseppe Ricci
Journal: Clinical Microbiology and Infection (2020)
Arthritogenic alphaviruses: epidemiological and clinical perspective on emerging arboviruses
Authors: Ali Zaid, Felicity J Burt, Xiang Liu, Yee Suan Poo, Keivan Zandi, Andreas Suhrbier, Scott C Weaver, Mauro M Texeira, Suresh Mahalingam
Journal: The Lancet Infectious Diseases (2020)
Abstract PR07: A systems biology approach to reprogramming drug-resistant breast cancer stem-like cells
Authors: Jeremy Worley, Hongxu Ding, Heeju Noh, Evan Paull, Erin Bush, Piero Dalerba, Peter Sims, Fil Dela Cruz, Andrew Kung, Andrea Califano
Journal: Cancer Research (2020)

Abstract Breast cancer stem-like cells (CSCs) are hypothesized to be a cause of poor outcome in patients, and are drug-resistant in vitro and in PDX mice. We performed plate-based single-cell RNA sequencing (scRNA-seq) on flow sorted fresh tumor samples. These data were analyzed using our metaVIPER algorithm, which infers protein activity in a manner that is robust to the effects of noise and gene dropout. metaVIPER identified known breast CSC regulators, and analysis with our OncoTreat algorithm predicted several FDA approved drugs that could reprogram the breast CSCs into a state resembling that of differentiated tumor cells. We tested two of these predictions, ivermectin and albendazole, in TNBC PDX mice, and performed scRNA-seq on fresh tumor samples after 14 days of treatment. The results were exciting, as measured by single-cell entropy or lineage marker analysis. Breast CSCs were reprogrammed as predicted, while a tumor treated with a traditional chemotherapeutic (paclitaxel) had a dramatically higher proportion of CSCs. These results suggested a therapy in which cells are cyclically reprogrammed and treated with a conventional cytotoxic drug. This reprogram-kill-repeat therapy is being tested in TNBC PDX mice. We believe that the strategy developed here will prove to be a powerful tool for understanding and manipulating cell-state in heterogeneous populations. Citation Format: Jeremy Worley, Hongxu Ding, Heeju Noh, Evan Paull, Erin Bush, Piero Dalerba, Peter Sims, Fil Dela Cruz, Andrew Kung, Andrea Califano. A systems biology approach to reprogramming drug-resistant breast cancer stem-like cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PR07.