Modeling adaptive therapy in non-muscle invasive bladder cancer
M. C. Ferrall-Fairbanks, G. J. Kimmel, M. Black, R. Bravo, O. Deac, P. Martinez, M. Myers, F. Nazari, A. Osojnik, H. Subramanian, Y. Viossat, F. Whiting, R. Li, K. M. Mann, P. M. Altrock
Abstract
Bladder cancer is the 9th most commonly diagnosed cancer. Nearly half of patients with early stage bladder cancer treated with the immune-stimulating agent BCG have disease recurrence, while 13% progress to invasive bladder cancer. Here we explored the potential of tumor mutational heterogeneity and the role of pro- and anti-inflammatory cytokines to identify different subtypes of bladder cancer that may predict therapeutic response to BCG. Further, we used mathematical modeling of dosing strategies to infer tumor response to varying doses and time schedules f BCG administration. As a proof-of-concept, present adaptive therapy scheduling of BCG as a viable strategy to control tumor size and minimize recurrence.
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