On Pi Day, the Breast Cancer Research Foundation (BCRF) is excited to announce a new partnership that links computational scientists with biologists. This partnership with the Jayne Koskinas Ted Giovanis (JKTG) Foundation for Health and Policy will include three new multi-institutional collaborations jointly funded to provide new insights into tumor growth and metastasis and the mechanisms of drug resistance. These groundbreaking studies will have the potential to substantially advance understanding of cancer biology and improve clinical outcomes.
In one of the projects, tumor biologist Dr. Daniele Gilkes and computational scientist Dr. Paul Macklin will collaborate to study how hypoxia, or low amounts of oxygen, a feature of most breast tumors influences breast cancer metastasis and poor outcomes. Drs. Gilkes and Macklin will utilize new technology to color-code cancer cells that have experienced low oxygen levels and track the cell during tumor progression. They will then use mathematical modeling approaches to combine experimental time course data analyzed with digital pathology of primary and metastatic sites to understand how the hypoxic conditions affect progression to metastasis.
Metastasis requires migratory behavior in order for a cancer cell to leave the primary tumor and the ability of the cell to revert back to a growth phase in distant organs. Another project combines the expertise of Dr. Andrew Ewald in cancer cell biology and the computational and mathematical modeling of Dr. Paul Newton, along with chemical engineering, gene network modeling, image analysis, and agent-based computational modeling to develop analysis and modeling tools to elucidate the molecular drivers of these transitions. This research builds on two concepts developed by the Ewald lab and others that cancer cells exist in distinct states specialized for growth or migration and metastasize in groups.
Deciphering Drug Resistance
Drug resistance is a key impediment to breast cancer therapy. While genetic mechanisms of drug resistance have been a focus of many studies, the ability of a cell to dynamically evade drugs through non-genetic means (called plasticity) is an often overlooked mechanism for why drugs may not be effective. Cellular plasticity gives rise to dynamic tumor heterogeneity through the generation of distinct subpopulations with diverse properties, including susceptibility to therapy.
Biologist Dr. Laura Heiser and mathematician Dr. Qing Nie will work together on a project that aims to understand cell plasticity and drug resistance. Their project will integrate experimental and modeling methods to overcome non-genetic mechanisms of drug resistance with the goal of identifying novel and more effective treatments for patients with breast cancer.
The concept of applying mathematics to science is not new; the ancient Greeks used math to understand the world around them. Mathematical modeling and theories allowed the Greeks to understand the movements of the Earth and moon, eventually giving way to modern astronomy and allowing us to land a man of the moon, which seemed impossible just decades before.
Similarly, the BCRF-JKTG Partnership to fund Applied Mathematics in Germinating Oncology Solutions (AMIGOS) grants – will move us one step closer to understanding the complexity of breast cancer that will hopefully lead to a cure.