A QSP model of prostate cancer immunotherapy to identify effective combination therapies.
Sci Rep
; 10(1): 9063, 2020 06 03.
Article
in En
| MEDLINE
| ID: mdl-32493951
ABSTRACT
Immunotherapy, by enhancing the endogenous anti-tumor immune responses, is showing promising results for the treatment of numerous cancers refractory to conventional therapies. However, its effectiveness for advanced castration-resistant prostate cancer remains unsatisfactory and new therapeutic strategies need to be developed. To this end, systems pharmacology modeling provides a quantitative framework to test in silico the efficacy of new treatments and combination therapies. In this paper we present a new Quantitative Systems Pharmacology (QSP) model of prostate cancer immunotherapy, calibrated using data from pre-clinical experiments in prostate cancer mouse models. We developed the model by using Ordinary Differential Equations (ODEs) describing the tumor, key components of the immune system, and seven treatments. Numerous combination therapies were evaluated considering both the degree of tumor inhibition and the predicted synergistic effects, integrated into a decision tree. Our simulations predicted cancer vaccine combined with immune checkpoint blockade as the most effective dual-drug combination immunotherapy for subjects treated with androgen-deprivation therapy that developed resistance. Overall, the model presented here serves as a computational framework to support drug development, by generating hypotheses that can be tested experimentally in pre-clinical models.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms, Castration-Resistant
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article