Cancer Systems Biology Consortium
Cancer is a complex disease system involving multiple molecular, genetic, and cellular events. From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external signals. These properties make cancer difficult to predict, prevent, and treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer. However, studies focused on the role of one gene have highlighted the need to understand cancers as integrated systems of genes, networks, and intercellular interactions.
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 birds eye view of the changing cancer ecosystem, thus allowing cancer biologists and oncologists to understand and predict how one alteration effects an entire tumor system. The multidisciplinary Cancer Systems Biology Consortium, which includes cancer biologists, engineers, mathematicians, physicists, and oncologists, aim to tackle the most perplexing issues in cancer to increase our understanding of tumor biology, treatment options, and patient outcome.
The Impact of Cancer Systems Biology on Cancer Research
There has been an explosion in the quantity of available experimental data from high-throughput technologies, such as genomic sequencing, transcriptomics, metabolomics, and proteomics. Additionally, targeted experiments on a smaller scale 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 knowledge. For ten years from 2004-2014, DCB supported the Integrative Cancer Biology Program (ICBP), a precursor to the current Cancer Systems Biology Consortium. The ICBP brought together cancer biologists and oncologists with computer scientists, mathematicians, and engineers to tackle important cancer questions including the identification of tumor master transcriptional regulators, the role of microRNAs in cancer progression and metastasis, the development of drug resistance in heterogeneous tumor contexts, and optimization of combination therapies for cancer treatment. It is envisioned that the past successes of cancer systems biology will encourage investigators to bring these tools to bear on emerging and difficult cancer questions that will require a systems approach to fully comprehend.
Funding Opportunities
The Cancer Systems Biology Consortium consists of specialized U01 Research Projects, U54 CSBC Research Centers, and a U24 Coordinating Center. An ongoing funding announcement for the CSBC U01 component can be found at the following link:
- Emerging Areas in Cancer Systems Biology (U01 Research Projects): PAR-16-131
Currently Funded Projects
Research Centers awarded grants in the first round of RFA-CA-15-014 include:
| Institution | Principal Investigators | Center Title |
|---|---|---|
| Columbia University | Dr. Andrea Califano and Dr. Barry Honig | Center for Cancer Systems Therapeutics (CaST) |
| Memorial Sloan Kettering Cancer Center | Dr. Christina Leslie and Dr. Alexander Rudensky | The CSBC Research Center for Cancer Systems Immunology at MSKCC |
| Stanford University | Dr. Sylvia Plevritis and Dr. Garry Nolan | Modeling the role of lymph node metastases in tumor-mediated immune suppression |
| Yale University | Dr. Andre Levchenko | Systems Analysis of Phenotypic Switch in Control of Cancer Invasion |
Research Centers awarded grants in the second round of RFA-CA-15-014 include:
| Institution | Principal Investigators | Center Title |
|---|---|---|
| City of Hope | Dr. Andrea Bild | Combating Subclonal Evolution of Resistant Cancer Phenotypes |
| Massachusetts Institute of Technology | Dr. Scott Manalis and Dr. Doug Lauffenburger | Quantitative and Functional Characterization of Therapeutic Resistance in Cancer |
| Oregon Health & Science University | Dr. Joe Gray, Dr. Emic Demir, Dr. Rosalie Sears, and Dr. Claire Tomlin | Measuring, Modeling and Controlling Heterogeneity |
| University of California, San Francisco | Dr. Nevan Krogan and Dr. Trey Ideker | Research Center for Cancer Systems Biology: Cancer Cell Map Initiative |
| University of Texas Health Science Center | Dr. Tim Huang, Dr. Victor Jin and Dr. Qianben Wang | Systems Analysis of Epigenomic Architecture in Cancer Progression |
Research Centers awarded grants in the third round of RFA-CA-15-014 include:
| Institution | Principal Investigators | Center Title |
|---|---|---|
| Arizona State University | Dr. Carlo Maley and Dr. Darryl Shibata | Arizona Cancer and Evolution Center (ACE) |
| Harvard Medical School | Dr. Peter Sorger | Center for Cancer Systems Pharmacology (CCSP) |
| University of California, Irvine | Dr. John Lowengrub, Dr. Arthur Lander and Dr. Marian Waterman | |
| Vanderbilt University | Dr. Vito Quaranta | Phenotype Heterogeneity and Dynamics in Small Cell Lung Cancer |
Research Projects awarded grants under PAR-16-131 include:
| Institution | Principal Investigators | Research Project Title |
|---|---|---|
| Dana-Farber Cancer Institute | Dr. Marc Vidal, Dr. Martha Bulyk, and Dr. Juan Fuxman | Rewiring of regulatory networks in breast cancer by transcription factor isoforms |
| Georgia Institute of Technology | Dr. Melissa Kemp, Dr. David Boothman, and Dr. Cristina Furdui | Model-Based Prediction of Redox-Modulated Responses to Cancer Treatments |
| H. Lee Moffitt Cancer Center & Research Institute | Dr. Alexander Anderson, Dr. Scott Antonia, and Dr. Robert Gatenby | Eco-Evolutionary dynamics of NSCLC to immunotherapy: Response and Resistance |
| Massachusetts Institute of Technology | Dr. Doug Lauffenburger, Dr. Wilhelm Haas and Dr. Kevin Haigis | Systems Approaches to Understanding the Relationships Between Genotype, Signaling, and Therapeutic Efficacy |
| Mayo Clinic Arizona | Dr. Kristin Swanson, Dr. Leland Hu, Dr. Joseph Mitchell, and Dr. Nhan Tran | Quantifying Multiscale Competitive Landscapes of Clonal Diversity in Glioblastoma |
| University of California, Los Angeles | Dr. Aaron Meyer, Dr. Eric Haura, and Dr. Forest White | Precision Lung Cancer Therapy Design through Multiplexed Adapter Measurement |
| University of Pennsylvania | Dr. Arjun Raj, Dr. Ravi Radhakrishnan, and Dr. Ashani Weeraratna | A plasticity and reprogramming paradigm for therapy resistance at the single cell level |
| University of Southern California | Dr. Stacey Finley and Dr. Shannon Mumenthaler | Multiscale systems biology modeling to exploit tumor-stromal metabolic crosstalk in colorectal cancer |
| University of Virginia | Dr. Kevin Janes | An Integrated Systems Approach for Incompletely Penetrant Onco-Phenotypes |
| Vanderbilt University | Dr. Vito Quaranta and Dr. Carlos Lopez | Phenotype Transitions in Small Cell Lung Cancer |
The Coordinating Center awarded for RFA-CA-15-015, which will contribute to the research missions of the Cancer Systems Biology Consortium and the Physical Sciences-Oncology Network is:
| Institution | Principal Investigator | Center Title |
|---|---|---|
| Sage Bionetworks | Dr. Justin Guinney | Coordination Center for Open Collaboration in Systems Biology |
Additional Information about the Consortium can be found on the CSBC page maintained by the Coordinating Center.
Several U01 Research Projects that were previously associated with the Integrative Cancer Biology Program were the initial members of the CSBC. These projects include those funded under the Bridging the Gap Between Cancer Mechanism and Population Science and the Collaborative Research in Integrative Cancer Biology U01 programs (no receipt dates remain for these programs).
Pre-application Webinar Materials
Slides for PAR-16-131
The National Cancer Institute (NCI) holds public pre-application webinars for the Funding Opportunity Announcement (FOA) PAR-16-131 entitled “Emerging Questions in Cancer Systems Biology (U01)”. NCI staff members involved in managing this program provide technical assistance to potential applicants by explaining the goals and objectives of the Cancer Systems Biology Consortium (CSBC) initiative and answer questions from attendees about the CSBC U01 Research Projects.
Slides from the webinar are now available: