Moffitt Cancer Center has long recognized the need to integrate mathematicians into cancer research to better understand the complex dynamics that govern cancer growth and treatment. The Integrated Mathematical Oncology (IMO) Department, established in 2007 and now consisting of six faculty members, integrates their skills with cancer biologists and oncologists in teams to use mathematical models to better understand cancer progression and treatment. This team driven science has led to pioneering work that has recently been acknowledged through a $10. 4 million award from the National Cancer Institute (NCI), designating Moffitt as one of the ten Physical Science – Oncology Centers (PSOC) in the United States. The other nine members of the NCI’sPhysical Sciences – Oncology Centers Program include Harvard, University of Pennsylvania, Columbia, Northwestern, MIT, Cornell, Houston Methodist, Johns Hopkins, and University of Minnesota.
The Moffitt PSOC is led by three highly interactive principle investigators - Alexander R. A. Anderson, Ph.D., chair of the IMO; Robert J. Gillies, Ph.D., chair of Cancer Imaging and Metabolism; and Robert A. Gatenby, M.D., chair of Radiology and a founder of this interdisciplinary effort. The PSOC focuses on evolution as the fundamental driving force of cancer development and the main reason that cancer therapy fails. A central goal of the center is to develop new strategies to prevent and treat cancer by exploiting Charles Darwin’s concept of natural selection.
“Cancer is a complex adaptive system that is driven by evolution of optimal traits that allows the cancer population to grow within its environment. When you treat a tumor with any therapy that causes tumor cell death, the tumor cells immediately begin to evolve resistance. This leads to treatment failure even when the initial response was excellent. Ultimately, the ability of tumor cells to evolve is the cause of death in people who die from cancer,” said Gatenby. “Our research investigates the evolutionary dynamics that drive cancers and uses our understanding of evolution against the cancer. But, this is a very complex process so we need sophisticated mathematical models and computer simulations to optimize treatments.”
The Moffitt PSOC is an integrating force that promotes interactions between experimentalists and mathematicians with an eye to developing new paradigms to prevent and treat cancer in the clinic.
“Cancer growth and therapy resistance are non-linear processes and therefore by definition non-intuitive. Our biggest hope of uncovering the key mechanisms that drive cancer is through the use of mathematical and computational models,” said Anderson. “Mathematical models are ideal tools for integrating the diverse components of cancer, with their ability to bridge multiple biological scales (from genes, proteins, pathways, cells, tissues, organs, populations), they can make novel predictions about the drivers of resistance, the likelihood of relapse or how best to tailor a therapy for a specific patient.”
“It is well recognized within our PSOC that models must be informed by and tested experimentally,” said Gilles. “We have been successfully accomplishing this kind of multidisciplinary team science for some time and have observed that even subtle perturbations can change a cancer’s direction from one that is highly lethal to a form that is more controllable. The new PSOC will be used to expand this paradigm to more cancers, with a goal of clinical trials to test the experimentally verified model predictions.”
The physical sciences oncology enterprise has generated a need for interdisciplinary scientists that feel equally at home in the wet lab as they do in the dry lab. These truly integrated scientists, however, are still very much a minority in the cancer community. A key element of the Moffitt-PSOC is to facilitate integrative science through appropriate education and outreach, since our PSOC involves the synergistic collaboration of clinicians, experimentalists and physical scientists. The overarching goal of the Moffitt PSOC training core is therefore to develop a framework to cross-train physical and clinical oncologists to facilitate translation of ecological and evolutionary principles into clinically testable treatment strategies by using specific mechanistic modeling. To this end, there are many needs and opportunities for training at this emerging interface that we will capitalize on in the Education and Outreach Component of our PSOC, co-lead by Alexander Anderson, Ph.D., and Heiko Enderling, Ph.D.
Leaders:
Alexander Anderson, Ph.D
Robert A. Gatenby, M.D.
Members:
John Cleveland, Ph.D.
Heiko Enderling, Ph.D.
Shari Pilon-Thomas, Ph.D.
Ken Shain, M.D.
Ariosto Silva, Ph.D.
Jingsong Zhang, M.D.
