ONCO-PS04

Characterizing Phenotypic Dynamics of Chemoresistance in Breast Cancer Cells

Wednesday, June 16 at 03:15pm (PDT)
Wednesday, June 16 at 11:15pm (BST)
Thursday, June 17 07:15am (KST)

SMB2021 SMB2021 Follow Wednesday (Thursday) during the "PS04" time block.
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Emily Yang

The University of Texas at Austin
"Characterizing Phenotypic Dynamics of Chemoresistance in Breast Cancer Cells"
Despite the continuing advancements in chemotherapy for breast cancer, the development of chemoresistance remains a significant cause of treatment failure. Intratumoral and inter-patient heterogeneity pose critical challenges to designing patient-specific optimized treatment plans. We posit that a mathematical understanding of chemoresistance dynamics could be key to developing clinically-feasible, successful treatment regimens. In this study, we develop a model that describes the effects of a standard neoadjuvant drug (doxorubicin) on a common breast cancer cell line (MCF7). We assume that the tumor is composed of two subpopulations: drug-resistant cells, which continue proliferating after treatment, and drug-sensitive cells, which gradually transition from proliferating to treatment-induced death. The model is calibrated with time-resolved microscopy data including variations in drug concentration, inter-treatment interval, and number of doses. Our results show that the model can recapitulate tumor growth dynamics in all of these scenarios (CCC>0.95). We observe that higher dosages resulted in significantly lower drug-resistant fraction and proliferation rates (p<0.05). Our results also show superior tumor control with a higher number of doses and shorter inter-treatment intervals (p<0.05). Thus, we believe that our model may contribute to our understanding of doxorubicin action and may guide the selection of therapeutic regimens that achieve optimal tumor control.










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