The central interest of Dr. Torres-Roca’s laboratory is in the development of a systems level understanding of the biological networks that regulate radiosensitivity. We apply and integrate engineering principles and mathematical modeling along with experimental cellular and molecular biology in an effort to elucidate the topology and function of the radiosensitivity network. In collaboration with ET members (Eschrich SA and Chen DT) his group has developed a mathematical approach to integrate genomics, genotype, tissue type and biological pathway interactions to identify radiation-specific biomarkers in a large dataset of cancer cell lines. This strategy has resulted in the identification of a novel and highly redundant genetic free-scale network with 10 central nodes that we have proposed as central in the determination of radiophenotype.
We applied this knowledge by developing in cell lines a gene expression linear regression model of cellular radiosensitivity based on the expression of the ten central network hubs. This model was subsequently independently validated as a predictor of response and prognosis in 277 patients in four different disease sites (breast, head and neck, rectal, esophagus), thus providing critical clinical validation for this approach. An NCI-sponsored prospective clinical trial is currently underway at Moffitt to further test the systems-based gene expression model as a predictor of clinical response in rectal and esophageal cancer patients treated with preoperative concurrent chemoradiation.
A major implication of this work is that mathematical modeling of cellular systems can lead to the development of technologies that can impact the clinic. Current efforts in the laboratory are aimed at integrating experimentally quantified cellular and clonogenic heterogeneity into computer-based virtual models of the clonogenic assay.