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Cancer Systems Biology Consortium (CSBC)

Cancer systems biology is uniquely poised to address the complexity associated with cancer through its unique integration of experimental biology and computational and mathematical analysis. Instead of viewing cancer through the lens of a single mutation or alteration, the goal of cancer systems biology is to provide a bird’s eye view of the changing cancer ecosystem, thus allowing cancer biologists and oncologists to understand and predict how one alteration affects an entire tumor system.

The multidisciplinary Cancer Systems Biology Consortium (CSBC), which includes cancer biologists, engineers, mathematicians, physicists, and oncologists, aims to tackle the most perplexing issues in cancer to increase our understanding of tumor biology, treatment options, and patient outcome.

Impact of Cancer Systems Biology Research

There has been an explosion in the quantity of available experimental data from high-throughput and single-cell technologies, such as genomic sequencing, transcriptomics, metabolomics, and proteomics. Additionally, targeted experiments on a smaller scale focused on a small number of genes and proteins have provided important information about complex interactions within and between cells. Systems analyses and predictive modeling are necessary to integrate across these datasets that span different length and time scales to convert them into actionable knowledge. 

DCB has supported development and growth of the cancer systems biology field since 2004. The Cancer Systems Biology Consortium (CSBC), DCB’s most recent effort to support cancer systems biology research, has three main goals:

Research Advances from the CSBC
  • Advance our understanding of mechanisms that underlie fundamental processes in cancer
  • Support the broad application of systems biology approaches in cancer research
  • Support the growth of a strong, stable, and diverse research community in cancer systems biology

An external expert panel evaluated the progress towards accomplishment of these goals in 2020. The panel found that CSBC investigators were contributing significant tools and knowledge towards our understanding of the tumor microenvironment, mechanisms of drug resistance and sensitivity, and cancer metastasis. A summary of CSBC progress and data describing the impact of the CSBC are publicly available, as is the external expert panel report.

It is envisioned that the success of cancer systems biology will encourage investigators to bring a systems biology approach to bear on emerging and difficult cancer questions that will require a systems approach to fully comprehend.

CSBC News

CSBC Investigator Highlights

New grants for CSBC Research Centers were awarded in Fall 2023.

Drs. Alexander Anderson and Robert Gatenby at Moffitt Cancer Center are investigating the role of spatiotemporal changes in tumor ecology during cancer progression and the evolution of therapeutic resistance in non-small cell lung cancer (NSCLC). 

The Center for Cancer Systems Therapeutics (CaST) at Columbia University, led by Drs. Andrea Califano and Barry Honig, is examining stable cell states and state transitions in tumor cells and the tumor microenvironment at the single-cell level. CaST is also identifying and targeting dependencies in cancer to inform mechanism-based combination therapy trials.

Drs. Sylvia Plevritis and Edgar Engleman at Stanford’s Systems Biology of Tumor-Immune-Stromal Interactions in Metastatic Progression Center are studying the role of lymph nodes in immune tolerance and distant metastases. They are also characterizing spatiotemporal changes at the primary tumor, lymph node, and distant sites associated with the onset and progression of metastasis.

The Mathematical Oncology Systems Analysis Imaging Center (MOSAIC) at the Mayo Clinic Arizona, led by Drs. Kristin Swanson and Peter Canoll, is examining the cellular composition of glioblastoma as it changes over time and space, identifying intercellular signals driving these changes, and determining mechanisms of brain tumor behavior and progression.

Drs. Forest White and Franziska Michor with the MIT CSBC Center are identifying dynamic interactions between glioma, neural, and immune cells that play a role in tumor dissemination, therapeutic response, and immunosuppression in glioblastoma. 
 

CSBC Social Media

CSBC research and funding opportunities are shared on Twitter: @NCIsysbio

CSBC Resources for Researchers

The Cancer Complexity Knowledge Portal contains the latest available resources generated through the CSBC. Information in the database includes:

  • Grants
  • Investigators
  • Publications
  • Datasets
  • Tools

CSBC Associate Membership

The CSBC offers the opportunity for Associate Membership in the consortium to those who are not currently funded through a CSBC award. Additional information, including eligibility criteria, expectations of associate members, and the application form can be found on the CSBC Associate Membership webpage. 

Contacts for the CSBC

For additional information about the CSBC, please contact Dr. Hannah Dueck or Dr. Monica Zamisch. 

Funded Projects

Research Centers for Cancer Systems Biology (U54s)

Institution Principal Investigator(s) Center Title
Arizona State University Carlo Maley, Darryl K. Shibata Arizona Cancer and Evolution Center (ACE)
Columbia University  Andrea Califano, Barry H. Honig Center for Cancer Systems Therapeutics (CaST)
Institute for Systems Biology James Heath Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics)
Massachusetts Institute of Technology Forest M. White, Franziska Michor Quantitative Systems Biology of Glioblastoma Cells and Their Interactions with the Neuronal and Immunological Milieu
Memorial Sloan Kettering Cancer Center Christina S. Leslie, Alexander Y. Rudensky The Center for Tumor-Immune Systems Biology at MSKCC
Mayo Clinic Arizona Kristin R. Swanson, Peter Canoll Mathematical Oncology Systems Analysis Imaging Center (MOSAIC)
Moffitt Cancer Center Alexander R.A. Anderson, Robert A. Gatenby The Delta Ecology of NSCLC Treatment
Stanford University  Sylvia K. Plevritis, Edgar G. Engleman Systems Biology of Tumor-Immune-Stromal Interactions in Metastatic Progression
University of California, Irvine John Lowengrub, Arthur D. Lander, Marian L. Waterman Complexity, Cooperation and Community in Cancer
University of California, San Francisco Nevan Krogan, Trey Ideker The Cancer Cell Map Initiative v2.0
University of Virginia Kevin A. Janes, Matthew J. Lazzara Systems Analysis of Stress-adapted Cancer Organelles (SASCO) Center
Vanderbilt University Vito Quaranta

Phenotype Heterogeneity and Dynamics in SCLC

Research Projects in Cancer Systems Biology (U01s)

Institution Principal Investigator(s) Center Title
Battelle Pacific Northwest Laboratories H. Steven Wiley, Wei-Jun Qian, Herbert M. Sauro Reverse Sensitivity Analysis for Identifying Predictive Proteomics Signatures of Cancer
Boston University Gerald V. Denis, Andrew Emili, Stefano Monti, Senthil K. Muthuswamy Multiscale Analysis of Metabolic Inflammation as a Driver of Breast Cancer
Children’s Hospital of Philadelphia Kai Tan, Sarah K. Tasian Towards Rational Design of Combination Therapeutic Targets
City of Hope Andrea H. Bild Mechanism of Estrogen Independent Proliferation in ER+ Breast Cancer Cells
City of Hope Peter P.H. Lee, Russell C. Rockne, Andrei Rodin Experimental-Computational Synthesis of Altered Immune Signaling in Breast Cancer
Columbia University Raul Rabadan, Teresa Palomero Single-Cell Characterization of Tumor and Microenvironment Co-evolution in Peripheral T-cell Lymphomas
Dana-Farber Cancer Institute Marc Vidal, Martha L. Bulyk, Juan I. Fuxman Bass Rewiring of Regulatory Networks in Breast Cancer by Transcription Factor Isoforms
Houston Methodist Research Institute Stephen T.C. Wong, Xiang Zhang Spatiotemporal Modeling of Cancer-Niche Interactions in Breast Cancer Bone Metastasis
John Hopkins University Laura D. Wood, Elana J. Fertig, Rachel Karchin Interrogation of the Impact of Selection on the Evolution of Human Pancreatic Cancer Precursor Lesions
Massachusetts Institute of Technology Ernest Fraenkel, Jill P. Mesirov Identifying Therapeutic Pathways Targeting Medulloblastoma-Immune Cell Interactions
Massachusetts Institute of Technology Forest M. White, Nataly Kravchenko-Balasha Identification of Adaptive Response Mechanisms in Breast Cancer by Information Theory and Proteomics
New York University School of Medicine Itai Yanai, Richard Mark White Identification and Characterization of Cancer Cell States by Novel Computational and Experimental Technologies
Oregon Health & Science University Gordon B. Mills, Anil Korkut, Han Liang Mechanistic Maps of Adaptive Responses to Therapeutic Stress to Optimize Combination Therapies
St. Jude Children’s Research Hospital Jiyang Yu, Jun J. Yang Clonal Therapy for Pediatric T-cell Acute Lymphoblastic Leukemia
Stanford University Andrew J. Gentles Systems analysis of mechanisms driving response to immunotherapy in clear cell cancers
University of Colorado, Denver James C. Costello, Scott D. Cramer Systems Analysis of Aggressive Prostate Cancer Pathology
University of Michigan Trachette Jackson Multiscale Computational Models Guided By Emerging Cellular Dynamics Quantification for Predicting Optimum Immune Checkpoint and Targeted Therapy Schedules
University of North Carolina, Chapel Hill Charles M. Perou, Timothy C. Elston Predictive Modeling of the EGFR-MAPK pathway for Triple Negative Breast Cancer Patients
University of Southern California Stacey D. Finley, Nicholas A. Graham Modeling based design of chimeric antigen receptors for Natural Killer cell-based immunotherapy
University of Southern California Stacey D. Finley, Paul T. Macklin, Shannon M. Mumenthaler Multiscale Systems Biology Modeling to Exploit Tumor-Stromal Metabolic Crosstalk in Colorectal Cancer
University of Texas, Austin Amy Brock, Thomas E. Yankeelov Systems Approaches to Understanding Subpopulation Heterogeneity in Therapeutic Resistance
University of Texas, MD Anderson Cancer Center  Humam Kadara, Linghua Wang Spatial and Temporal Tumor-Immune Co-Evolution and Interactions that Model Lung Adenocarcinoma Development
University of Virginia Matthew J. Lazzara Optimal Control Models of Epithelial-Mesenchymal Transition for the Design of Pancreas Cancer Combination Therapy
Yale University Kathryn Miller-Jensen, Marcus W. Bosenberg Systems Analysis of Cell-Cell Communication Networks and Immune Activity in the Melanoma Tumor Microenvironment

Multi-Consortia Coordinating Center (U24)

Institution Principal Investigator(s) Center Title
Sage Bionetworks Julie Bletz, James A. Eddy Multi-Consortia Coordinating Center (MC2 Center) for Cancer Biology: Building Interdisciplinary Scientific Communities, Coordinating Impactful Resource Sharing, and Advancing Cancer Research

Past Projects

Research Centers for Cancer Systems Biology (U54s)

Institution Principal Investigator(s) Center Title
City of Hope Andrea H. Bild Combating Subclonal Evolution of Resistant Cancer Phenotypes
Columbia University Andrea Califano, Barry H. Honig  Centers for Cancer Systems Therapeutics (CaST)
Harvard Medical School Peter K. Sorger Systems Pharmacology of Therapeutic and Adverse Responses to Immune Checkpoint and Small Molecule Drugs
Massachusetts Institute of Technology Scott R. Manalis, Douglas A. Lauffenburger Quantitative and Functional Characterization of Therapeutic Resistance in Cancer
Memorial Sloan Kettering Cancer Center Christina S. Leslie, Alexander Y. Rudensky The CSBC Research Center for Cancer Systems Immunology at MSKCC
Oregon Health & Science University Laura M. Heiser, Emek Demir, Gordon B. Mills, Rosalie C. Sears, Claire J. Tomlin Measuring, Modeling and Controlling Heterogeneity
University of California, San Francisco Nevan Krogan, Trey Ideker Research Center for Cancer Systems Biology: Cancer Cell Map Initiative
University of Texas Health Science Center at San Antonio Tim H.M. Huang, Victor Jin, Qianben Wang Systems Analysis of Epigenomic Architecture in Cancer Progression
Yale University Andre Levchenko Systems Analysis of Phenotypic Switch in Control of Cancer Invasion

Research Projects in Cancer Systems Biology (U01s)

Institution Principal Investigator(s) Center Title
Georgia Institute of Technology Melissa L. Kemp, Cristina M. Furdui Model-based Prediction of Redox-Modulated Responses to Cancer Treatments
Massachusetts Institute of Technology Douglas A. Lauffenburger, Wilhelm Haas, Kevin Haigis Systems Approaches to Understanding the Relationships Between Genotype, Signaling, and Therapeutic Efficacy
Mayo Clinic Arizona Kristin R. Swanson, Leland Hu, Nhan L. Tran Quantifying Multiscale Competitive Landscapes of Clonal Diversity in Glioblastoma
Moffitt Cancer Center Alexander R.A. Anderson, Scott J. Antonia, Robert A. Gatenby Eco-Evolutionary dynamics of NSCLC to immunotherapy: Response and Resistance
University of California, Los Angeles Aaron S. Meyer, Eric B. Haura Precision Lung Cancer Therapy Design Through Multiplexed Adapter Measurement
University of Pennsylvania Arjun Raj, Ravi Radhakrishnan, Ashani T. Weeraratna A Plasticity and Reprogramming Paradigm for Therapy Resistance at the Single Cell Level
University of Virginia Kevin A. Janes An Integrated Systems Approach for Incompletely Penetrant Onco-phenotypes
Vanderbilt University Vito Quaranta, Carlos F. Lopez Phenotype Transitions in Small Cell Lung Cancer

Coordinating Center for the CSBC (U24)

Institution Principal Investigator(s) Center Title
Sage Bionetworks Julie Bletz Coordination Center for Open Collaboration in Systems Biology
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