Moffitt Receives $10.4 Million to Develop Treatment Strategies to Overcome Drug Resistance in Lung Cancer
TAMPA, Fla. — The Center of Excellence for Evolutionary Therapy at Moffitt Cancer Center has received a $10.4 million grant to study the eco-evolutionary dynamics responsible for non-small cell lung cancer growth and treatment resistance. The five-year Cancer Systems Biology Consortium Research Center grant (U54CA274507) will support two multitier research projects, two research support cores and an innovative outreach core.
“While many see cancer evolution as a sequence of genetic changes or mutations, our team believes that to truly understand cancer evolution, you must also consider its dynamic ecology,” said Alexander Anderson, Ph.D., co-principal investigator of the grant, director of the Center of Excellence for Evolutionary Therapy and chair of the Integrated Mathematical Oncology Department.
Their work suggests cancer cells respond to and modify both the physical microenvironment and a variety of host cells, and these changes in ecology, referred to as Delta (∆)-Ecology, are key to understanding tumor progression and the response to therapy.
The two research projects will focus on different ∆-Ecology dynamics — immune and stromal — in the presence of different driver mutations (RAS, EGFR, ALK) for which targeted therapy is available. The immune dynamic aims to understand and exploit the immune response to targeted inhibitors in combination with immunotherapy. The stromal dynamic will quantify and manipulating the reactive stromal framework within cells that facilitates drug resistance. Each project will begin with a deep analysis of patient samples, followed by the development of mathematical models and testing in experimental models leading to readily translatable treatment options. Through an integrated team science approach, bringing together mathematicians, clinicians, biologists, immunologists, pathologists and evolutionary biologists, they will develop and test novel treatment strategies for non-small cell lung cancer that exploit evolution rather than ignoring it.
Their work will be supported by two newly created research cores. A Mathematical Core will facilitate the development of spatial and nonspatial models of the eco-evolutionary processes occurring during the growth and treatment of lung cancer. An Ecology Core will serve as a data repository and ecological analysis engine to develop and apply spatial ecological models to patient samples before and during treatment.
Non-small cell lung cancer is the most common type of lung cancer, accounting for 80% to 85% of all diagnoses. While this form of lung cancer progresses more slowly, nearly 40% of patients will have metastatic disease by the time they are diagnosed.
“Targeted therapies focusing on driver mutations have been successful in treating non-small cell lung cancer, but eventually the tumor cells will evolve and become resistant. Our projects aim to uncover novel therapeutic strategies that can suppress that evolution of resistance,” said Robert Gatenby, M.D., co-principal investigator of the grant, co-director of the Center of Excellence for Evolutionary Therapy and research department chair of the Diagnostic Imaging and Interventional Radiology Program.
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 56 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 8,500 team members, Moffitt has an economic impact in the state of $2.4 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter, Instagram and YouTube.