Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer.

ABSTRACT: In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an 'evolutionary stable therapy', within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve

SUBMITTER: Cunningham J 

PROVIDER: S-EPMC7723267 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature