The Columbia University Center for Cancer Systems Therapeutics (CaST) was created in 2016 as one of four inaugural centers in the National Cancer Institute’s Cancer Systems Biology Consortium (CSBC). The CSBC initiative aims to address challenges of complexity in basic and translational cancer research through the use of experimental biology combined with in silico modeling, multi-dimensional data analysis, and systems engineering.

Building on model-driven perspectives and methods developed over the past 10 years, CaST has assembled a multidisciplinary community of Columbia University investigators who together are developing a novel framework for understanding how malignant tumors evade treatment, induce disease progression, and develop drug resistance.  

Addressing these challenges requires an entirely novel conceptual framework capable of identifying and disabling the regulatory machinery at the heart of cancer cell state initiation and maintenance. Using a combination of computational and experimental methods developed at Columbia, we are studying this machinery across multiple levels of granularity — including interactions between tumors and their microenvironment as well as single-cell heterogeneity and plasticity — representing the full, systems-wide complexity of the tumor phenotype.  Our goals include:

  • Developing systematic, network-based approaches to elucidate the regulatory logic that is responsible for maintaining cancer cell state . Going beyond the genetic alterations that initiate cancer, we focus on delineating the modular regulatory architectures (tumor checkpoints) and specific proteins within these modules (master regulators) that are specific to cancer cells and are essential for tumor homeostasis.
  • Dissecting time-dependent mechanisms of genetic and epigenetic reprogramming of individual cancer cells that lead to cancer-state transitions, including drug resistance and disease progression . Our approach involves leveraging innovative computational models for characterizing subclonal genomic cell populations and using single-cell data from primary tumors and patient-derived xenografts to elucidate the mechanisms presiding over tumor plasticity.
  • Developing novel methods for prioritizing compounds and compound combinations capable of abrogating tumorigenesis in vivo . These methods target tumor checkpoints with the goal of inducing irreversible collapse of the mechanisms that preside over the stability of cancer cell state.

To achieve these goals CaST has assembled a multidisciplinary scientific team comprising faculty from several departments and institutes at Columbia University. CaST investigators are experts in the development of computational methods for analyzing functional and structural data, high-throughput technologies for single-cell profiling, high-throughput genetic and pharmacological screening, experimental methods for studying tumor evolution in vivo, and software development,.

In addition, CaST conducts outreach  to disseminate the software and methods developed by the Center, foster discussion on related issues within the larger scientific community, support community-based research efforts and challenges such as the Dialogue on Reverse Engineering Assessment and Methods (DREAM), and mentor young scientists to encourage a new generation of investigators to become involved.

Ultimately, CaST aims to use the remarkable opportunities that systems biology now offers to identify more effective, widely applicable strategies for precision cancer medicine.