Optimization of personalized therapies for anticancer treatment

BMC Systems Biology

Alexei Vazquez¹ 

[1] Department of Radiation Oncology and Center for Systems Biology, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 195 Little Albany St, New Brunswick, NJ 08903, USA

关键词: Combinatorial therapy;    Targeted therapy;    Personalized medicine;    Cancer;   

Others  :  1142943
DOI  :  10.1186/1752-0509-7-31

 received in 2012-07-03, accepted in 2013-03-26,  发布年份 2013

【 摘 要 】

Background

As today, there are hundreds of targeted therapies for the treatment of cancer, many of which have companion biomarkers that are in use to inform treatment decisions. If we would consider this whole arsenal of targeted therapies as a treatment option for every patient, very soon we will reach a scenario where each patient is positive for several markers suggesting their treatment with several targeted therapies. Given the documented side effects of anticancer drugs, it is clear that such a strategy is unfeasible.

Results

Here, we propose a strategy that optimizes the design of combinatorial therapies to achieve the best response rates with the minimal toxicity. In this methodology markers are assigned to drugs such that we achieve a high overall response rate while using personalized combinations of minimal size. We tested this methodology in an in silico cancer patient cohort, constructed from in vitro data for 714 cell lines and 138 drugs reported by the Sanger Institute. Our analysis indicates that, even in the context of personalized medicine, combinations of three or more drugs are required to achieve high response rates. Furthermore, patient-to-patient variations in pharmacokinetics have a significant impact in the overall response rate. A 10 fold increase in the pharmacokinetics variations resulted in a significant drop the overall response rate.

Conclusions

The design of optimal combinatorial therapy for anticancer treatment requires a transition from the one-drug/one-biomarker approach to global strategies that simultaneously assign makers to a catalog of drugs. The methodology reported here provides a framework to achieve this transition.

【 授权许可】

   
2013 Vazquez; licensee BioMed Central Ltd.

【 图 表 】

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