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 2022.

Dr. James Heath et al. at the Institute for Systems Biology Center are using spatiotemporal tumor analytics to guide combination treatments of targeted inhibitors and immunotherapy for cancer.

The MSKCC Center, led by Drs. Christina Leslie and Alexander Rudensky, is utilizing systems biology tools to improve the understanding of tumor-immune interactions in contexts where current immunotherapies fail and developing new strategies for enhancing responses to treatment.

Dr. Nevan Krogan, Dr. Trey Ideker, et al. at the UCSF/UCSD Center are applying systems approaches to comprehensively map the molecular networks that underlie cancer. These maps may inform cancer precision medicine.

The University of Virginia Center, led by Drs. Kevin Janes and Matthew Lazzara, is performing a systems analysis of stress-adapted cancer organelles. It aims to advance the understanding of subcellular adaptations that take place to subvert stresses that occur in response to cancer-causing mutations.

CSBC Digital Media

Learn more about the CSBC via the following digital media platforms:

CSBC Website
CSBC 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)
City of Hope	Andrea H. Bild	Combating Subclonal Evolution of Resistant Cancer Phenotypes
Institute for Systems Biology	James Heath	Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics)
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 Center for Tumor-Immune Systems Biology 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, 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 Texas Health Science Center at San Antonio	Tim H.M. Huang, Victor Jin, Qianben Wang	Systems Analysis of Epigenomic Architecture in Cancer Progression
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
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
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 California, Los Angeles	Aaron S. Meyer, Eric B. Haura	Precision Lung Cancer Therapy Design Through Multiplexed Adapter Measurement
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 Pennsylvania	Arjun Raj, Ravi Radhakrishnan, Ashani T. Weeraratna	A Plasticity and Reprogramming Paradigm for Therapy Resistance at the Single Cell Level
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
Vanderbilt University	Vito Quaranta, Carlos F. Lopez	Phenotype Transitions in Small Cell Lung Cancer
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
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
Memorial Sloan Kettering Cancer Center	Christina S. Leslie, Alexander Y. Rudensky	The CSBC Research Center for Cancer Systems Immunology at MSKCC
University of California, San Francisco	Nevan Krogan, Trey Ideker	Research Center for Cancer Systems Biology: Cancer Cell Map Initiative
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
University of Virginia	Kevin A. Janes	An Integrated Systems Approach for Incompletely Penetrant Onco-phenotypes

Coordinating Center for the CSBC (U24)

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