Wednesday 25th April 2018 at 1.00pm in MATH-103 Seminar to by Presented by Pavitra Kannan (University of Oxford)

Title: Interactions between heterogeneous tumour cell populations affect growth and radiation response of prostate spheroids

Abstract: Prostate cancer is a heterogeneous, multi-clonal disease that is commonly treated with external beam radiotherapy. Local recurrence in prostate cancer remains a challenge in treatment. Theoretical studies have suggested that better tumour control can be achieved by accounting for biological heterogeneity in radiation treatment plans. We sought to provide biological evidence for this hypothesis by determining whether heterogeneous populations with different radiation sensitivities have altered growth and radiation response in prostate cancer. We found that radiation resistant cells enhance the survival and radiation resistance of sensitive cells in 3D but not in 2D. Mathematical modelling revealed that these phenotypic changes are consistent with competitive interactions between resistant and sensitive populations. The observed changes are mediated both by hypoxic microenvironment and by transferred factors between the cell populations, because we found that adaptation to hypoxia and transferred factors released in hypoxic conditions enhance survival of the sensitive populations. Our ongoing work investigates the biological mechanism of competition and whether accounting for cellular heterogeneity in treatment plans can lead to more accurate predictions of radiation response.