Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer.
PLoS One
; 15(12): e0243386, 2020.
Article
em En
| MEDLINE
| ID: mdl-33290430
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 tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proliferação de Células
/
Neoplasias de Próstata Resistentes à Castração
/
Docetaxel
/
Androstenos
Tipo de estudo:
Clinical_trials
/
Guideline
Limite:
Humans
/
Male
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos