Institute for Applied Cancer Science
Comprehensive Cancer Biology and Translational Medicine
A comprehensive understanding of a specific protein's role in the initiation and maintenance of cancer lies at the heart of all IACS drug discovery projects. The biology teams use a full array of complementary genetic and chemical probes to validate novel therapeutic targets and understand the role of a specific target in cancer. Each team works to develop an in-depth understanding of how, and in what specific cellular and genetic contexts, a deregulated protein can highjack the normal cellular pathways to drive aberrant cellular proliferation. With this knowledge in hand, teams work to develop and leverage appropriate preclinical models to evaluate the impact of therapeutic intervention in specific disease settings. Specifically, which patients would specifically benefit from treatment with a novel agent, and how tumors may adapt to treatment so that strategies to address drug resistance can be developed.
All biology and translational medicine efforts leverage a large arsenal of preclinical models and are supported by cutting-edge genomic and bioinformatic capabilities. Scientists employ network modeling to explore the connectivity and redundancy of target candidates, and use functional genomics to assess a target’s cancer relevance. Our preclinical model repertoire includes a large and fully characterized panel of cancer cell lines, clinically annotated and genomically characterized patient-derived xenograft models, as well as sophisticated genetically engineered mouse models of human cancer. Particular emphasis is given to the genetic and pathophysiological contexts of in vivo disease models, as tumors are considered “neo-organs.” Additional focus is placed on understanding the biological and genotypic context in which the selected targets for drug discovery are rate limiting and cooperate.
Associated with drug development work is a deep focus on biomarkers both for the identification of which patients may be responsive to treatment, as well as ensuring the novel agent is inhibiting the targeted aberrant pathway(s). Biomarker identification and validation are an integral part of the IACS target assessment and drug discovery programs and will accelerate the time from target discovery to clinical proof of concept. Clinical samples inform on disease relevance and patient stratification leveraging genomic and proteomic annotation and patient outcome data, as seen in the figure that demonstrates copy number alterations, aneuploidy and gene re-arrangements/translocations. Proximal and distal pharmacodynamics biomarkers are discovered early and validated using a combination of pharmacological and genetic tools. IACS develops quantitative assays to enable in vivo pharmacokinetic, pharmacodynamic and efficacy studies, as well as guide the development of drug dosing paradigms and combinations with standard-of-care.
Insights gained from preclinical models in vitro and in vivo will inform biomarker-driven single agent and combination trials conducted in appropriately selected patient subpopulations. Working closely with the MD Anderson's departments and disease centers, the project teams always have line-of-sight to the clinic, and are always considering where our projects will have the most clinical impact.
We believe our seamless integration of drug discovery biology with world-class translational and clinical expertise provides a powerful platform for developing the next generation of novel anticancer therapies.