ArticleThe Prostate2018
A two-drug combination simulation study for metastatic castrate resistant prostate cancer.
Article in The Prostate, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A two-drug combination simulation study for metastatic castrate resistant prostate cancer.The Prostate · 2018Article
- Structure-based assessment and network analysis of targeting 14-3-3 proteins in prostate cancer.Molecular cancer · 2018Article
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Authors and funding
2 authors.
Funding
Abstract
backgroundProstate cancer often evolves resistance to androgen deprivation therapy leading to a lethal metastatic castrate-resistant form. Besides androgen independence, subpopulations of the tumor are genetically heterogeneous. With the advent of tumor genome sequencing we asked which has the greater influence on reducing tumor size: genetic background, heterogeneity, or drug potency?
methodsA previously developed theoretical evolutionary dynamics model of stochastic branching processes is applied to compute the probability of tumor eradication with two targeted drugs. Publicly available data sets were surveyed to parameterize the model.
resultsOur calculations reveal that the greatest influence on successful treatment is the genetic background including the number of mutations overcoming resistance. Another important criteria is the tumor size at which it is still possible to achieve tumor eradication, for example, 2-4 cm large tumors have at best a 10% probability to be eradicated when 50 mutations can confer resistance to each drug.
conclusionOverall, this study finds that genetic background and tumor heterogeneity are more important than drug potency in treating mCRPC. It also points toward identifying metastatic sites early using biochemical assays and/or dPET.
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