School of Mechanical Engineering Prof. David S. Rumschitzki CUNY

School of Mechanical Engineering Seminar
Wednesday, March 13, 2019 at 14:00
Wolfson Building of Mechanical Engineering, Room 206

Tumor dormancy and recurrence: theory & experiment for tumor growth, regression & metastasis

Prof. David S. Rumschitzki

  Department of Chemical Engineering, The City College of New York

PhD programs in Chemistry and Biology, Graduate School and University Center, City University of New York

Department 0f Medicine (Cardiology), Columbia Presbyterian Medical Center, Columbia University

Collaborators: Adeyinka Lesi (PhD student), Silja Heilmann (Postdoc), Richard M. White      (Professor at Memorial Sloan Kettering Cancer Center)

Certain types of cancer including breast cancer and melanoma can recur many years after apparently successful treatment. It is a mystery how tumor cells can remain dormant for many years, avoid eradication by the immune system and then reactivate after many years. We present a population balance model to describe how the size distribution of an ensemble of tumors from many patients evolves in time due to mitosis, cell death and metastasis. A transformation recasts the dynamic interplay between tumor growth and shrinkage in these equations into the form of an advective-diffusion equation in tumor size space. These new equations predict and thus provide a plausible mechanism for tumor dormancy and recurrence for certain relationships amongst the three model parameters. After showing that our model easily fits data sets on tumor size distributions in the literature, we present new, far more refined gender- and immune status-segregated data on the zebrafish melanoma. We show that our model also describes these data very well. Study of gender-segregated cohorts shows gender-dependent parameter only appears in the host-dependent parameter describing tumor shrinkage; it is far more size-dependent in females than in males, which may be relevant for gender differences in human melanoma outcomes. Fortunately for the fish, their model parameters do not predict recurrence over fish lifetimes. However, the model guides our current experiments by instructing us on how to try to perturb fish immunity to bring fish parameters into the range where we should be able to observe fish melanoma dormancy and recurrence. There are claims in the literature that a mouse model of breast cancer can show dormancy and recurrence. We are beginning a collaboration at the Technion Rambam using this mouse model to test our mathematical model and to see we find dormancy and recurrence theoretically, experimentally or both.