Connecting the Microenvironmental Niche to Treatment Response in Ovarian Cancer

Strobl, M.; Wicker, M.; Adhikarla, V.; Shockey, A.; Lakatos, E.; Pooladvand, P.; Schenck, R.; Saputro, L.; Gatenby, C.; Koppens, M.; Cruz Garcia, S.; Wenham, R.; Damaghi, M.; Gallaher, J. A.

doi:10.1101/452052

bioRxiv · 10.1101/452052

Connecting the Microenvironmental Niche to Treatment Response in Ovarian Cancer

Strobl, M.·Wicker, M.·Adhikarla, V.·Shockey, A.·Lakatos, E.·Pooladvand, P.·Schenck, R.·Saputro, L.·Gatenby, C.·Koppens, M.·Cruz Garcia, S.·Wenham, R.·Damaghi, M.·Gallaher, J. A.

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Abstract

Ovarian cancer has the highest mortality rate of all gynecologic cancers, which may be attributed to an often late stage diagnosis, when the cancer is already metastatic, and rapid development of treatment resistance. We propose that the metastatic disease could be better characterized by observing interactions within the microenvironmental niche of the primary site that shapes the tumors early phenotypic progression. We present a mechanistic mathematical model of ovarian cancer that considers spatial interactions between tumor cells and several key stromal components. We demonstrate how spatial biomarker imaging data from the primary tumor can be analyzed to define a patient-specific microenvironment in the mathematical model. We then show preliminary results, using this model, that demonstrate how differences in the niche composition of a tumor affects phenotypic evolution and treatment response.

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Strobl, M., Wicker, M., Adhikarla, V., Shockey, A., Lakatos, E., Pooladvand, P., Schenck, R., Saputro, L., Gatenby, C., Koppens, M., Cruz Garcia, S., Wenham, R., Damaghi, M., Gallaher, J. A.. 2018-10-24. Connecting the Microenvironmental Niche to Treatment Response in Ovarian Cancer. https://doi.org/10.1101/452052

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